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Chemical Structure| 850140-73-7 Chemical Structure| 850140-73-7

Structure of Afatinib dimaleate
CAS No.: 850140-73-7

Chemical Structure| 850140-73-7

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Afatinib (BIBW 2992) dimaleate is an orally active, potent, and irreversible dual specificity inhibitor of the ErbB family (EGFR and HER2), with IC50 values of 0.5 nM, 0.4 nM, 10 nM, and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M, and HER2, respectively. It is used in research on esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC), and gastric cancer.

Synonyms: BIBW 2992MA2; Afatinib (maleate); BIBW 2992

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Product Details of Afatinib dimaleate

CAS No. :850140-73-7
Formula : C32H33ClFN5O11
M.W : 718.08
SMILES Code : O=C(NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1O[C@@H]4COCC4)/C=C/CN(C)C.O=C(O)/C=C\C(O)=O.O=C(O)/C=C\C(O)=O
Synonyms :
BIBW 2992MA2; Afatinib (maleate); BIBW 2992
MDL No. :MFCD25974239

Safety of Afatinib dimaleate

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Afatinib dimaleate

RTK
JAK-STAT

Isoform Comparison

Biological Activity

Target
  • EGFR/ErbB1

    EGFR (wt), IC50:0.5 nM

    EGFR (L858R/T790M), IC50:0.4 nM

  • HER2/ErbB2

    HER2, IC50:14 nM

  • HER2

    HER2, IC50:14 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
NCI-H2170 5 nM-2 μM 6 months Establish afatinib-resistant cell lines to study resistance mechanisms PMC5980184
H2073-ASV cell lines 10 nM 2 weeks Evaluate the growth inhibitory effect of afatinib on EGFR Ex20Ins mutant cells PMC5932243
H2073-SVD cell lines 10 nM 2 weeks Evaluate the growth inhibitory effect of afatinib on EGFR Ex20Ins mutant cells PMC5932243
NCI-H1781 5 nM-0.4 μM 6 months Establish afatinib-resistant cell lines to study resistance mechanisms PMC5980184
ICC11 cell line 100 nM 5 days To evaluate the effect of Afatinib in combination with FGFR inhibitors on cell death induction in FGFR2 fusion-positive ICC cell lines. Results showed that Afatinib significantly enhanced the cell death induction effect of FGFR inhibitors. PMC9064956
ICC10-6 cell line 100 nM 5 days To evaluate the effect of Afatinib in combination with FGFR inhibitors on cell death induction in FGFR2 fusion-positive ICC cell lines. Results showed that Afatinib significantly enhanced the cell death induction effect of FGFR inhibitors. PMC9064956
ICC21 cell line 100 nM 5 days To evaluate the effect of Afatinib in combination with FGFR inhibitors on cell death induction in FGFR2 fusion-positive ICC cell lines. Results showed that Afatinib significantly enhanced the cell death induction effect of FGFR inhibitors. PMC9064956
ICC13-7 cell line 100 nM 5 days To evaluate the effect of Afatinib in combination with FGFR inhibitors on cell death induction in FGFR2 fusion-positive ICC cell lines. Results showed that Afatinib significantly enhanced the cell death induction effect of FGFR inhibitors. PMC9064956
Hs746T cell line 0.001, 0.01, 0.5, or 1 μM 20 min Hs746T cells did not respond to afatinib, and MET amplification was identified as a potential resistance factor. PMC5891041
MKN7 cell line 0.001, 0.01, 0.5, or 1 μM 20 min Trastuzumab treatment resulted in a moderate, nonsignificant decrease in HER2 phosphorylation. Afatinib slightly decreased the phosphorylation of EGFR and HER2 (nonsignificantly). PMC5891041
MKN1 cell line 0.001, 0.01, 0.5, or 1 μM 20 min Trastuzumab treatment had no effect in the cell line MKN1. Phosphorylation of EGFR was increased by EGF treatment and decreased by afatinib treatment (nonsignificantly). PMC5891041
NCI-N87 cell line 0.001, 0.01, 0.5, or 1 μM 20 min Afatinib alone or in combination with trastuzumab influenced HER kinases in all cell lines; that is, the effects of monotherapy and combination therapy were transduced to the intracellular kinase network. PMC5891041
Human ESCC cell lines TE-10 0, 10 nM, 100 nM, 1 μM 48 h To evaluate the anti-proliferative activity of Afatinib on TE-10 cells and its effects on EGFR downstream signaling molecules. Results showed that Afatinib effectively inhibited EGFR phosphorylation. PMC6114252
NSCLC cell lines Calu3 5 nM-2 μM 6 months Establish afatinib-resistant cell lines to study resistance mechanisms PMC5980184
Human ESCC cell lines TE-1 cell line 0, 10 nM, 100 nM, 1 μM 48 h To evaluate the anti-proliferative activity of Afatinib on TE-1 cells and its effects on EGFR downstream signaling molecules. Results showed that Afatinib effectively inhibited EGFR phosphorylation but failed to significantly suppress pERK in insensitive cells. PMC6114252
Human ESCC cell lines KYSE510 0, 10 nM, 100 nM, 1 μM 48 h To evaluate the anti-proliferative activity of Afatinib on KYSE510 cells and its effects on EGFR downstream signaling molecules. Results showed that Afatinib effectively inhibited EGFR phosphorylation but failed to significantly suppress pS6 and pERK in insensitive cells. PMC6114252
Human ESCC cell lines KYSE140 0, 10 nM, 100 nM, 1 μM 48 h To evaluate the anti-proliferative activity of Afatinib on KYSE140 cells and its effects on EGFR downstream signaling molecules. Results showed that Afatinib effectively inhibited EGFR phosphorylation and significantly suppressed pS6 and pERK in sensitive cells. PMC6114252
Human ESCC cell lines KYSE450 0, 10 nM, 100 nM, 1 μM 48 h To evaluate the anti-proliferative activity of Afatinib on KYSE450 cells and its effects on EGFR downstream signaling molecules. Results showed that Afatinib effectively inhibited EGFR phosphorylation and significantly suppressed pS6 and pERK in sensitive cells. PMC6114252
Human ESCC cell lines EC109 0, 10 nM, 100 nM, 1 μM 48 h To evaluate the anti-proliferative activity of Afatinib on EC109 cells and its effects on EGFR downstream signaling molecules. Results showed that Afatinib effectively inhibited EGFR phosphorylation and significantly suppressed pS6 and pERK in sensitive cells. PMC6114252
ESTDAB105 2 µM 72 h Evaluate the effect of combination therapy on BRAF/NRAS wild-type melanoma cells, results showed significant reduction in cell viability. PMC6737096
ESTDAB102 2 µM 72 h Evaluate the effect of combination therapy on NRAS-mutant melanoma cells, results showed significant reduction in cell viability. PMC6737096
SkMel2 cells 2 µM 72 h Evaluate the effect of combination therapy on NRAS-mutant melanoma cells, results showed significant reduction in cell viability. PMC6737096
A375VR4 cells 2 µM 72 h Evaluate the effect of combination therapy on drug-resistant melanoma cells, results showed significant reduction in cell viability. PMC6737096
A375 melanoma cells 2 µM 72 h Evaluate the effect of Afatinib and Crizotinib combination therapy on melanoma cell viability, results showed significant reduction in cell viability. PMC6737096
TNBC cell lines BT20 4.66 ± 0.32 µM(IC50) 5 days To evaluate the antiproliferative effects of afatinib on TNBC cell lines, BT20 showed an IC50 value of 4.66 ± 0.32 µM for afatinib. PMC6987485
TNBC cell lines HDQP1 0.04 ± 0.01 µM(IC50) 5 days To evaluate the antiproliferative effects of afatinib on TNBC cell lines, HDQP1 showed an IC50 value of 0.04 ± 0.01 µM for afatinib. PMC6987485
TNBC cell lines HCC1937 0.90 ± 0.28 µM(IC50) 5 days To evaluate the antiproliferative effects of afatinib on TNBC cell lines, HCC1937 showed an IC50 value of 0.90 ± 0.28 µM for afatinib. PMC6987485

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice ICC21 subcutaneous xenograft model Oral gavage 15 mg/kg Daily for 21 days To evaluate the in vivo efficacy of Afatinib in combination with FGFR inhibitors in FGFR2 fusion-positive ICC models. Results showed that combination treatment significantly induced tumor regression. PMC9064956
NOD/SCID mice ESCC PDX models Oral gavage 15 mg/kg Once daily for 21 days To evaluate the anti-tumor effects of Afatinib in ESCC PDX models. Results showed that Afatinib significantly inhibited tumor growth, with TGI ranging from 82.65% to 118.4%. PMC6114252
Mice Xenograft model Oral 20 mg/kg Daily for 14 days Evaluate the effect of combination therapy on melanoma xenograft model, results showed significant reduction in tumor growth rate. PMC6737096
SCID mice H2073-SVD and H2073-ASV xenograft models Oral gavage 7.5 or 20 mg/kg Once daily for 14 days Evaluate the tumor growth inhibitory effect of afatinib on EGFR Ex20Ins mutant tumors, results showed afatinib at 7.5 mg/kg was ineffective in H2073-SVD and H2073-ASV models PMC5932243
Mice WT C57BL/6J mice Oral gavage 25 mg/kg For 2 weeks To study the effects of ErbB signaling inhibition on VEGF-B–induced cardiac hypertrophy, results showed that afatinib inhibited VEGF-B–induced phosphorylation of Akt and Erk. PMC6553980
BALB/c-nu/nu female mice Calu3-ARS xenograft model Oral 20 mg/kg 6 days per week for 3 weeks Evaluate the efficacy of combined afatinib and crizotinib treatment on afatinib-resistant tumors with MET amplification PMC5980184
Nude mice Non-small cell lung cancer patient-derived xenograft (PDX) models Oral 15 mg/kg 5 days on, 2 days off for 4 cycles To evaluate the efficacy of low-dose combination therapy in overcoming therapy resistance, results showed complete suppression of tumor growth in all PDX models PMC8763947
CB17/lcr-PrkdcSCID/Crl mice HCC1806 xenograft model Oral gavage 10 mg/kg 5 days on, 2 days off, for 21-23 days To evaluate the antitumor efficacy of afatinib combined with dasatinib in the HCC1806 xenograft model, the combination treatment significantly delayed tumor growth. PMC6987485
NSG mice SUIT2 orthotopic model Intraperitoneal 5 mg/kg Once daily for 10 days Evaluate the antitumor efficacy of afatinib combined with MRTX1133, showing significant reduction in tumor volume PMC10502451

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02131259 Carcinoma, Non-Small-Cell Lung COMPLETED 2016-12-28 Boehringer Ingelheim Investiga... More >>tional Site 145, Adachi Tokyo, Japan|Boehringer Ingelheim Investigational Site 429, Aira Kagoshima, Japan|Boehringer Ingelheim Investigational Site 64, Aizuwakamatsu Fukushima, Japan|Boehringer Ingelheim Investigational Site 44, Akita Akita, Japan|Boehringer Ingelheim Investigational Site 45, Akita Akita, Japan|Boehringer Ingelheim Investigational Site 46, Akita Akita, Japan|Boehringer Ingelheim Investigational Site 47, Akita Akita, Japan|Boehringer Ingelheim Investigational Site 333, Amagasaki Hyogo, Japan|Boehringer Ingelheim Investigational Site 266, Anjo Aichi, Japan|Boehringer Ingelheim Investigational Site 27, Aomori Aomori, Japan|Boehringer Ingelheim Investigational Site 28, Aomori Aomori, Japan|Boehringer Ingelheim Investigational Site 127, Asahi Chiba, Japan|Boehringer Ingelheim Investigational Site 128, Asahi Chiba, Japan|Boehringer Ingelheim Investigational Site 18, Asahikawa Hokkaido, Japan|Boehringer Ingelheim Investigational Site 19, Asahikawa Hokkaido, Japan|Boehringer Ingelheim Investigational Site 20, Asahikawa Hokkaido, Japan|Boehringer Ingelheim Investigational Site 21, Asahikawa Hokkaido, Japan|Boehringer Ingelheim Investigational Site 198, Atsugi Kanagawa, Japan|Boehringer Ingelheim Investigational Site 294, Ayabe Kyoto, Japan|Boehringer Ingelheim Investigational Site 142, Bunkyo Tokyo, Japan|Boehringer Ingelheim Investigational Site 143, Bunkyo Tokyo, Japan|Boehringer Ingelheim Investigational Site 144, Bunkyo Tokyo, Japan|Boehringer Ingelheim Investigational Site 112, Chiba Chiba, Japan|Boehringer Ingelheim Investigational Site 113, Chiba Chiba, Japan|Boehringer Ingelheim Investigational Site 114, Chiba Chiba, Japan|Boehringer Ingelheim Investigational Site 115, Chiba Chiba, Japan|Boehringer Ingelheim Investigational Site 116, Chiba Chiba, Japan|Boehringer Ingelheim Investigational Site 117, Chiba Chiba, Japan|Boehringer Ingelheim Investigational Site 402, Chikugo Fukuoka, Japan|Boehringer Ingelheim Investigational Site 16, Chitose Hokkaido, Japan|Boehringer Ingelheim Investigational Site 132, Chiyoda Tokyo, Japan|Boehringer Ingelheim Investigational Site 133, Chiyoda Tokyo, Japan|Boehringer Ingelheim Investigational Site 134, Chiyoda Tokyo, Japan|Boehringer Ingelheim Investigational Site 135, Chuo Tokyo, Japan|Boehringer Ingelheim Investigational Site 136, Chuo Tokyo, Japan|Boehringer Ingelheim Investigational Site 234, Chuo Yamanashi, Japan|Boehringer Ingelheim Investigational Site 235, Chuo Yamanashi, Japan|Boehringer Ingelheim Investigational Site 48, Daisen Akita, Japan|Boehringer Ingelheim Investigational Site 147, Edogawa Tokyo, Japan|Boehringer Ingelheim Investigational Site 148, Edogawa Tokyo, Japan|Boehringer Ingelheim Investigational Site 173, Fuchu Tokyo, Japan|Boehringer Ingelheim Investigational Site 257, Fuji Shizuoka, Japan|Boehringer Ingelheim Investigational Site 260, Fujieda Shizuoka, Japan|Boehringer Ingelheim Investigational Site 97, Fujioka Gumma, Japan|Boehringer Ingelheim Investigational Site 203, Fujisawa Kanagawa, Japan|Boehringer Ingelheim Investigational Site 111, Fukaya Saitama, Japan|Boehringer Ingelheim Investigational Site 231, Fukui Fukui, Japan|Boehringer Ingelheim Investigational Site 232, Fukui Fukui, Japan|Boehringer Ingelheim Investigational Site 393, Fukuoka Fukuoka, Japan|Boehringer Ingelheim Investigational Site 394, Fukuoka Fukuoka, Japan|Boehringer Ingelheim Investigational Site 395, Fukuoka Fukuoka, Japan|Boehringer Ingelheim Investigational Site 396, Fukuoka Fukuoka, Japan|Boehringer Ingelheim Investigational Site 399, Fukuoka Fukuoka, Japan|Boehringer Ingelheim Investigational Site 58, Fukushima Fukushima, Japan|Boehringer Ingelheim Investigational Site 59, Fukushima Fukushima, Japan|Boehringer Ingelheim Investigational Site 60, Fukushima Fukushima, Japan|Boehringer Ingelheim Investigational Site 356, Fukuyama Hiroshima, Japan|Boehringer Ingelheim Investigational Site 357, Fukuyama Hiroshima, Japan|Boehringer Ingelheim Investigational Site 121, Funabashi Chiba, Japan|Boehringer Ingelheim Investigational Site 251, Gifu Gifu, Japan|Boehringer Ingelheim Investigational Site 252, Gifu Gifu, Japan|Boehringer Ingelheim Investigational Site 432, Ginowan Okinawa, Japan|Boehringer Ingelheim Investigational Site 321, Habikino Osaka, Japan|Boehringer Ingelheim Investigational Site 29, Hachinohe Aomori, Japan|Boehringer Ingelheim Investigational Site 30, Hachinohe Aomori, Japan|Boehringer Ingelheim Investigational Site 176, Hachioji Tokyo, Japan|Boehringer Ingelheim Investigational Site 209, Hadano Kanagawa, Japan|Boehringer Ingelheim Investigational Site 3, Hakodate Hokkaido, Japan|Boehringer Ingelheim Investigational Site 349, Hamada Shimane, Japan|Boehringer Ingelheim Investigational Site 261, Hamamatsu Shizuoka, Japan|Boehringer Ingelheim Investigational Site 367, Hatsukaichi Hiroshima, Japan|Boehringer Ingelheim Investigational Site 107, Hidaka Saitama, Japan|Boehringer Ingelheim Investigational Site 76, Higashiibaraki Ibaraki, Japan|Boehringer Ingelheim Investigational Site 53, Higashiokitama Yamagata, Japan|Boehringer Ingelheim Investigational Site 54, Higashiokitama Yamagata, Japan|Boehringer Ingelheim Investigational Site 318, Higashiosaka Osaka, Japan|Boehringer Ingelheim Investigational Site 339, Himeji Hyogo, Japan|Boehringer Ingelheim Investigational Site 316, Hirakata Osaka, Japan|Boehringer Ingelheim Investigational Site 317, Hirakata Osaka, Japan|Boehringer Ingelheim Investigational Site 208, Hiratsuka Kanagawa, Japan|Boehringer Ingelheim Investigational Site 31, Hirosaki Aomori, Japan|Boehringer Ingelheim Investigational Site 32, Hirosaki Aomori, Japan|Boehringer Ingelheim Investigational Site 359, Hiroshima Hiroshima, Japan|Boehringer Ingelheim Investigational Site 360, Hiroshima Hiroshima, Japan|Boehringer Ingelheim Investigational Site 361, Hiroshima Hiroshima, Japan|Boehringer Ingelheim Investigational Site 362, Hiroshima Hiroshima, Japan|Boehringer Ingelheim Investigational Site 363, Hiroshima Hiroshima, Japan|Boehringer Ingelheim Investigational Site 364, Hiroshima Hiroshima, Japan|Boehringer Ingelheim Investigational Site 79, Hitachi Ibaraki, Japan|Boehringer Ingelheim Investigational Site 77, Hitachinaka Ibaraki, Japan|Boehringer Ingelheim Investigational Site 78, Hitachinaka Ibaraki, Japan|Boehringer Ingelheim Investigational Site 312, Ibaraki Osaka, Japan|Boehringer Ingelheim Investigational Site 131, Ichihara Chiba, Japan|Boehringer Ingelheim Investigational Site 120, Ichikawa Chiba, Japan|Boehringer Ingelheim Investigational Site 246, Iida Nagano, Japan|Boehringer Ingelheim Investigational Site 247, Iida Nagano, Japan|Boehringer Ingelheim Investigational Site 309, Ikeda Osaka, Japan|Boehringer Ingelheim Investigational Site 248, Ina Nagano, Japan|Boehringer Ingelheim Investigational Site 118, Inzai Chiba, Japan|Boehringer Ingelheim Investigational Site 105, Iruma Saitama, Japan|Boehringer Ingelheim Investigational Site 428, Isa Kagoshima, Japan|Boehringer Ingelheim Investigational Site 407, Isahaya Nagasaki, Japan|Boehringer Ingelheim Investigational Site 281, Ise Mie, Japan|Boehringer Ingelheim Investigational Site 95, Isesaki Gumma, Japan|Boehringer Ingelheim Investigational Site 168, Itabashi Tokyo, Japan|Boehringer Ingelheim Investigational Site 65, Iwaki Fukushima, Japan|Boehringer Ingelheim Investigational Site 368, Iwakuni Yamaguchi, Japan|Boehringer Ingelheim Investigational Site 17, Iwamizawa Hokkaido, Japan|Boehringer Ingelheim Investigational Site 324, Izumi Osaka, Japan|Boehringer Ingelheim Investigational Site 348, Izumo Shimane, Japan|Boehringer Ingelheim Investigational Site 255, Izunokuni Shizuoka, Japan|Boehringer Ingelheim Investigational Site 213, Joetsu Niigata, Japan|Boehringer Ingelheim Investigational Site 214, Joetsu Niigata, Japan|Boehringer Ingelheim Investigational Site 289, Joyo Kyoto, Japan|Boehringer Ingelheim Investigational Site 422, Kagoshima Kagoshima, Japan|Boehringer Ingelheim Investigational Site 423, Kagoshima Kagoshima, Japan|Boehringer Ingelheim Investigational Site 424, Kagoshima Kagoshima, Japan|Boehringer Ingelheim Investigational Site 425, Kagoshima Kagoshima, Japan|Boehringer Ingelheim Investigational Site 426, Kagoshima Kagoshima, Japan|Boehringer Ingelheim Investigational Site 262, Kakegawa Shizuoka, Japan|Boehringer Ingelheim Investigational Site 340, Kakogawa Hyogo, Japan|Boehringer Ingelheim Investigational Site 201, Kamakura Kanagawa, Japan|Boehringer Ingelheim Investigational Site 202, Kamakura Kanagawa, Japan|Boehringer Ingelheim Investigational Site 130, Kamogawa Chiba, Japan|Boehringer Ingelheim Investigational Site 223, Kanazawa Ishikawa, Japan|Boehringer Ingelheim Investigational Site 224, Kanazawa Ishikawa, Japan|Boehringer Ingelheim Investigational Site 225, Kanazawa Ishikawa, Japan|Boehringer Ingelheim Investigational Site 226, Kanazawa Ishikawa, Japan|Boehringer Ingelheim Investigational Site 227, Kanazawa Ishikawa, Japan|Boehringer Ingelheim Investigational Site 74, Kasama Ibaraki, Japan|Boehringer Ingelheim Investigational Site 343, Kashihara Nara, Japan|Boehringer Ingelheim Investigational Site 123, Kashiwa Chiba, Japan|Boehringer Ingelheim Investigational Site 124, Kashiwa Chiba, Japan|Boehringer Ingelheim Investigational Site 125, Kashiwa Chiba, Japan|Boehringer Ingelheim Investigational Site 104, Kasukabe Saitama, Japan|Boehringer Ingelheim Investigational Site 106, Kawagoe Saitama, Japan|Boehringer Ingelheim Investigational Site 100, Kawaguchi Saitama, Japan|Boehringer Ingelheim Investigational Site 99, Kawaguchi Saitama, Japan|Boehringer Ingelheim Investigational Site 182, Kawasaki Kanagawa, Japan|Boehringer Ingelheim Investigational Site 183, Kawasaki Kanagawa, Japan|Boehringer Ingelheim Investigational Site 184, Kawasaki Kanagawa, Japan|Boehringer Ingelheim Investigational Site 185, Kawasaki Kanagawa, Japan|Boehringer Ingelheim Investigational Site 186, Kawasaki Kanagawa, Japan|Boehringer Ingelheim Investigational Site 42, Kesennuma Miyagi, Japan|Boehringer Ingelheim Investigational Site 129, Kisarazu Chiba, Japan|Boehringer Ingelheim Investigational Site 325, Kishiwada Osaka, Japan|Boehringer Ingelheim Investigational Site 326, Kishiwada Osaka, Japan|Boehringer Ingelheim Investigational Site 377, Kita Kagawa, Japan|Boehringer Ingelheim Investigational Site 110, Kitaadachi Saitama, Japan|Boehringer Ingelheim Investigational Site 387, Kitakyushu Fukuoka, Japan|Boehringer Ingelheim Investigational Site 388, Kitakyushu Fukuoka, Japan|Boehringer Ingelheim Investigational Site 389, Kitakyushu Fukuoka, Japan|Boehringer Ingelheim Investigational Site 390, Kitakyushu Fukuoka, Japan|Boehringer Ingelheim Investigational Site 391, Kitakyushu Fukuoka, Japan|Boehringer Ingelheim Investigational Site 392, Kitakyushu Fukuoka, Japan|Boehringer Ingelheim Investigational Site 25, Kitami Hokkaido, Japan|Boehringer Ingelheim Investigational Site 26, Kitami Hokkaido, Japan|Boehringer Ingelheim Investigational Site 180, Kiyose Tokyo, Japan|Boehringer Ingelheim Investigational Site 181, Kiyose Tokyo, Japan|Boehringer Ingelheim Investigational Site 327, Kobe Hyogo, Japan|Boehringer Ingelheim Investigational Site 328, Kobe Hyogo, Japan|Boehringer Ingelheim Investigational Site 329, Kobe Hyogo, Japan|Boehringer Ingelheim Investigational Site 330, Kobe Hyogo, Japan|Boehringer Ingelheim Investigational Site 331, Kobe Hyogo, Japan|Boehringer Ingelheim Investigational Site 383, Kochi Kochi, Japan|Boehringer Ingelheim Investigational Site 384, Kochi Kochi, Japan|Boehringer Ingelheim Investigational Site 385, Kochi Kochi, Japan|Boehringer Ingelheim Investigational Site 386, Kochi Kochi, Japan|Boehringer Ingelheim Investigational Site 174, Kodaira Tokyo, Japan|Boehringer Ingelheim Investigational Site 233, Kofu Yamanashi, Japan|Boehringer Ingelheim Investigational Site 397, Koga Fukuoka, Japan|Boehringer Ingelheim Investigational Site 398, Koga Fukuoka, Japan|Boehringer Ingelheim Investigational Site 179, Komae Tokyo, Japan|Boehringer Ingelheim Investigational Site 228, Komatsu Ishikawa, Japan|Boehringer Ingelheim Investigational Site 61, Koriyama Fukushima, Japan|Boehringer Ingelheim Investigational Site 62, Koriyama Fukushima, Japan|Boehringer Ingelheim Investigational Site 63, Koriyama Fukushima, Japan|Boehringer Ingelheim Investigational Site 103, Koshigaya Saitama, Japan|Boehringer Ingelheim Investigational Site 149, Koto Tokyo, Japan|Boehringer Ingelheim Investigational Site 150, Koto Tokyo, Japan|Boehringer Ingelheim Investigational Site 108, Kumagaya Saitama, Japan|Boehringer Ingelheim Investigational Site 109, Kumagaya Saitama, Japan|Boehringer Ingelheim Investigational Site 411, Kumamoto Kumamoto, Japan|Boehringer Ingelheim Investigational Site 413, Kumamoto Kumamoto, Japan|Boehringer Ingelheim Investigational Site 414, Kumamoto Kumamoto, Japan|Boehringer Ingelheim Investigational Site 415, Kumamoto Kumamoto, Japan|Boehringer Ingelheim Investigational Site 352, Kurashiki Okayama, Japan|Boehringer Ingelheim Investigational Site 355, Kurashiki Okayama, Japan|Boehringer Ingelheim Investigational Site 365, Kure Hiroshima, Japan|Boehringer Ingelheim Investigational Site 366, Kure Hiroshima, Japan|Boehringer Ingelheim Investigational Site 24, Kushiro Hokkaido, Japan|Boehringer Ingelheim Investigational Site 278, Kuwana Mie, Japan|Boehringer Ingelheim Investigational Site 285, Kyoto Kyoto, Japan|Boehringer Ingelheim Investigational Site 286, Kyoto Kyoto, Japan|Boehringer Ingelheim Investigational Site 287, Kyoto Kyoto, Japan|Boehringer Ingelheim Investigational Site 288, Kyoto Kyoto, Japan|Boehringer Ingelheim Investigational Site 291, Kyoto Kyoto, Japan|Boehringer Ingelheim Investigational Site 292, Kyoto Kyoto, Japan|Boehringer Ingelheim Investigational Site 293, Kyoto Kyoto, Japan|Boehringer Ingelheim Investigational Site 177, Machida Tokyo, Japan|Boehringer Ingelheim Investigational Site 91, Maebashi Gumma, Japan|Boehringer Ingelheim Investigational Site 92, Maebashi Gumma, Japan|Boehringer Ingelheim Investigational Site 93, Maebashi Gumma, Japan|Boehringer Ingelheim Investigational Site 94, Maebashi Gumma, Japan|Boehringer Ingelheim Investigational Site 119, Matsudo Chiba, Japan|Boehringer Ingelheim Investigational Site 346, Matsue Shimane, Japan|Boehringer Ingelheim Investigational Site 347, Matsue Shimane, Japan|Boehringer Ingelheim Investigational Site 241, Matsumoto Nagano, Japan|Boehringer Ingelheim Investigational Site 242, Matsumoto Nagano, Japan|Boehringer Ingelheim Investigational Site 243, Matsumoto Nagano, Japan|Boehringer Ingelheim Investigational Site 244, Matsumoto Nagano, Japan|Boehringer Ingelheim Investigational Site 249, Matsumoto Nagano, Japan|Boehringer Ingelheim Investigational Site 250, Matsumoto Nagano, Japan|Boehringer Ingelheim Investigational Site 280, Matsusaka Mie, Japan|Boehringer Ingelheim Investigational Site 378, Matsuyama Ehime, Japan|Boehringer Ingelheim Investigational Site 379, Matsuyama Ehime, Japan|Boehringer Ingelheim Investigational Site 381, Matsuyama Ehime, Japan|Boehringer Ingelheim Investigational Site 158, Meguro Tokyo, Japan|Boehringer Ingelheim Investigational Site 159, Meguro Tokyo, Japan|Boehringer Ingelheim Investigational Site 416, Minamata Kumamoto, Japan|Boehringer Ingelheim Investigational Site 137, Minato Tokyo, Japan|Boehringer Ingelheim Investigational Site 138, Minato Tokyo, Japan|Boehringer Ingelheim Investigational Site 139, Minato Tokyo, Japan|Boehringer Ingelheim Investigational Site 140, Minato Tokyo, Japan|Boehringer Ingelheim Investigational Site 171, Mitaka Tokyo, Japan|Boehringer Ingelheim Investigational Site 172, Mitaka Tokyo, Japan|Boehringer Ingelheim Investigational Site 75, Mito Ibaraki, Japan|Boehringer Ingelheim Investigational Site 419, Miyazaki Miyazaki, Japan|Boehringer Ingelheim Investigational Site 420, Miyazaki Miyazaki, Japan|Boehringer Ingelheim Investigational Site 421, Miyazaki Miyazaki, Japan|Boehringer Ingelheim Investigational Site 315, Moriguchi Osaka, Japan|Boehringer Ingelheim Investigational Site 33, Morioka Iwate, Japan|Boehringer Ingelheim Investigational Site 34, Morioka Iwate, Japan|Boehringer Ingelheim Investigational Site 282, Moriyama Shiga, Japan|Boehringer Ingelheim Investigational Site 283, Moriyama Shiga, Japan|Boehringer Ingelheim Investigational Site 5, Muroran Hokkaido, Japan|Boehringer Ingelheim Investigational Site 284, Nagahama Shiga, Japan|Boehringer Ingelheim Investigational Site 274, Nagakute Aichi, Japan|Boehringer Ingelheim Investigational Site 236, Nagano Nagano, Japan|Boehringer Ingelheim Investigational Site 237, Nagano Nagano, Japan|Boehringer Ingelheim Investigational Site 238, Nagano Nagano, Japan|Boehringer Ingelheim Investigational Site 210, Nagaoka Niigata, Japan|Boehringer Ingelheim Investigational Site 211, Nagaoka Niigata, Japan|Boehringer Ingelheim Investigational Site 212, Nagaoka Niigata, Japan|Boehringer Ingelheim Investigational Site 405, Nagasaki Nagasaki, Japan|Boehringer Ingelheim Investigational Site 406, Nagasaki Nagasaki, Japan|Boehringer Ingelheim Investigational Site 267, Nagoya Aichi, Japan|Boehringer Ingelheim Investigational Site 268, Nagoya Aichi, Japan|Boehringer Ingelheim Investigational Site 269, Nagoya Aichi, Japan|Boehringer Ingelheim Investigational Site 270, Nagoya Aichi, Japan|Boehringer Ingelheim Investigational Site 271, Nagoya Aichi, Japan|Boehringer Ingelheim Investigational Site 272, Nagoya Aichi, Japan|Boehringer Ingelheim Investigational Site 80, Naka Ibaraki, Japan|Boehringer Ingelheim Investigational Site 167, Nakano Tokyo, Japan|Boehringer Ingelheim Investigational Site 341, Nara Nara, Japan|Boehringer Ingelheim Investigational Site 122, Narashino Chiba, Japan|Boehringer Ingelheim Investigational Site 39, Natori Miyagi, Japan|Boehringer Ingelheim Investigational Site 169, Nerima Tokyo, Japan|Boehringer Ingelheim Investigational Site 170, Nerima Tokyo, Japan|Boehringer Ingelheim Investigational Site 215, Niigata Niigata, Japan|Boehringer Ingelheim Investigational Site 216, Niigata Niigata, Japan|Boehringer Ingelheim Investigational Site 217, Niigata Niigata, Japan|Boehringer Ingelheim Investigational Site 218, Niigata Niigata, Japan|Boehringer Ingelheim Investigational Site 382, Niihama Ehime, Japan|Boehringer Ingelheim Investigational Site 334, Nishinomiya Hyogo, Japan|Boehringer Ingelheim Investigational Site 335, Nishinomiya Hyogo, Japan|Boehringer Ingelheim Investigational Site 336, Nishinomiya Hyogo, Japan|Boehringer Ingelheim Investigational Site 22, Obihiro Hokkaido, Japan|Boehringer Ingelheim Investigational Site 23, Obihiro Hokkaido, Japan|Boehringer Ingelheim Investigational Site 253, Ogaki Gifu, Japan|Boehringer Ingelheim Investigational Site 417, Oita Oita, Japan|Boehringer Ingelheim Investigational Site 418, Oita Oita, Japan|Boehringer Ingelheim Investigational Site 350, Okayama Okayama, Japan|Boehringer Ingelheim Investigational Site 351, Okayama Okayama, Japan|Boehringer Ingelheim Investigational Site 353, Okayama Okayama, Japan|Boehringer Ingelheim Investigational Site 264, Okazaki Aichi, Japan|Boehringer Ingelheim Investigational Site 265, Okazaki Aichi, Japan|Boehringer Ingelheim Investigational Site 178, Ome Tokyo, Japan|Boehringer Ingelheim Investigational Site 358, Onomichi Hiroshima, Japan|Boehringer Ingelheim Investigational Site 295, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 296, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 297, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 298, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 299, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 300, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 301, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 302, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 303, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 304, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 305, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 306, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 307, Osaka Osaka, Japan|Boehringer Ingelheim Investigational Site 43, Osaki Miyagi, Japan|Boehringer Ingelheim Investigational Site 35, Oshu Iwate, Japan|Boehringer Ingelheim Investigational Site 96, Ota Gumma, Japan|Boehringer Ingelheim Investigational Site 153, Ota Tokyo, Japan|Boehringer Ingelheim Investigational Site 154, Ota Tokyo, Japan|Boehringer Ingelheim Investigational Site 155, Ota Tokyo, Japan|Boehringer Ingelheim Investigational Site 156, Ota Tokyo, Japan|Boehringer Ingelheim Investigational Site 4, Otaru Hokkaido, Japan|Boehringer Ingelheim Investigational Site 85, Otawara Tochigi, Japan|Boehringer Ingelheim Investigational Site 70, Ryugasaki Ibaraki, Japan|Boehringer Ingelheim Investigational Site 403, Saga Saga, Japan|Boehringer Ingelheim Investigational Site 204, Sagamihara Kanagawa, Japan|Boehringer Ingelheim Investigational Site 205, Sagamihara Kanagawa, Japan|Boehringer Ingelheim Investigational Site 206, Sagamihara Kanagawa, Japan|Boehringer Ingelheim Investigational Site 207, Sagamihara Kanagawa, Japan|Boehringer Ingelheim Investigational Site 322, Sakai Osaka, Japan|Boehringer Ingelheim Investigational Site 323, Sakai Osaka, Japan|Boehringer Ingelheim Investigational Site 56, Sakata Yamagata, Japan|Boehringer Ingelheim Investigational Site 57, Sakata Yamagata, Japan|Boehringer Ingelheim Investigational Site 239, Saku Nagano, Japan|Boehringer Ingelheim Investigational Site 126, Sakura Chiba, Japan|Boehringer Ingelheim Investigational Site 338, Sanda Hyogo, Japan|Boehringer Ingelheim Investigational Site 10, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 11, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 12, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 13, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 14, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 15, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 1, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 2, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 7, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 8, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 9, Sapporo Hokkaido, Japan|Boehringer Ingelheim Investigational Site 409, Sasebo Nagasaki, Japan|Boehringer Ingelheim Investigational Site 410, Sasebo Nagasaki, Japan|Boehringer Ingelheim Investigational Site 73, Sashima Ibaraki, Japan|Boehringer Ingelheim Investigational Site 427, Satsumasendai Kagoshima, Japan|Boehringer Ingelheim Investigational Site 36, Sendai Miyagi, Japan|Boehringer Ingelheim Investigational Site 37, Sendai Miyagi, Japan|Boehringer Ingelheim Investigational Site 38, Sendai Miyagi, Japan|Boehringer Ingelheim Investigational Site 40, Sendai Miyagi, Japan|Boehringer Ingelheim Investigational Site 275, Seto Aichi, Japan|Boehringer Ingelheim Investigational Site 219, Shibata Niigata, Japan|Boehringer Ingelheim Investigational Site 98, Shibukawa Gumma, Japan|Boehringer Ingelheim Investigational Site 157, Shibuya Tokyo, Japan|Boehringer Ingelheim Investigational Site 408, Shimabara Nagasaki, Japan|Boehringer Ingelheim Investigational Site 430, Shimajiri Okinawa, Japan|Boehringer Ingelheim Investigational Site 369, Shimonoseki Yamaguchi, Japan|Boehringer Ingelheim Investigational Site 371, Shimonoseki Yamaguchi, Japan|Boehringer Ingelheim Investigational Site 372, Shimonoseki Yamaguchi, Japan|Boehringer Ingelheim Investigational Site 83, Shimotsuga Tochigi, Japan|Boehringer Ingelheim Investigational Site 84, Shimotsuga Tochigi, Japan|Boehringer Ingelheim Investigational Site 87, Shimotsuke Tochigi, Japan|Boehringer Ingelheim Investigational Site 88, Shimotsuke Tochigi, Japan|Boehringer Ingelheim Investigational Site 151, Shinagawa Tokyo, Japan|Boehringer Ingelheim Investigational Site 152, Shinagawa Tokyo, Japan|Boehringer Ingelheim Investigational Site 160, Shinjuku Tokyo, Japan|Boehringer Ingelheim Investigational Site 161, Shinjuku Tokyo, Japan|Boehringer Ingelheim Investigational Site 162, Shinjuku Tokyo, Japan|Boehringer Ingelheim Investigational Site 163, Shinjuku Tokyo, Japan|Boehringer Ingelheim Investigational Site 164, Shinjuku Tokyo, Japan|Boehringer Ingelheim Investigational Site 165, Shinjuku Tokyo, Japan|Boehringer Ingelheim Investigational Site 166, Shinjuku Tokyo, Japan|Boehringer Ingelheim Investigational Site 41, Shiogama Miyagi, Japan|Boehringer Ingelheim Investigational Site 258, Shizuoka Shizuoka, Japan|Boehringer Ingelheim Investigational Site 259, Shizuoka Shizuoka, Japan|Boehringer Ingelheim Investigational Site 102, Soka Saitama, Japan|Boehringer Ingelheim Investigational Site 310, Suita Osaka, Japan|Boehringer Ingelheim Investigational Site 311, Suita Osaka, Japan|Boehringer Ingelheim Investigational Site 146, Sumida Tokyo, Japan|Boehringer Ingelheim Investigational Site 332, Sumoto Hyogo, Japan|Boehringer Ingelheim Investigational Site 256, Sunto Shizuoka, Japan|Boehringer Ingelheim Investigational Site 245, Suwa Nagano, Japan|Boehringer Ingelheim Investigational Site 175, Tachikawa Tokyo, Japan|Boehringer Ingelheim Investigational Site 141, Taito Tokyo, Japan|Boehringer Ingelheim Investigational Site 376, Takamatsu Kagawa, Japan|Boehringer Ingelheim Investigational Site 222, Takaoka Toyama, Japan|Boehringer Ingelheim Investigational Site 337, Takarazuka Hyogo, Japan|Boehringer Ingelheim Investigational Site 89, Takasaki Gumma, Japan|Boehringer Ingelheim Investigational Site 90, Takasaki Gumma, Japan|Boehringer Ingelheim Investigational Site 313, Takatsuki Osaka, Japan|Boehringer Ingelheim Investigational Site 314, Takatsuki Osaka, Japan|Boehringer Ingelheim Investigational Site 254, Takayama Gifu, Japan|Boehringer Ingelheim Investigational Site 342, Tenri Nara, Japan|Boehringer Ingelheim Investigational Site 86, Tochigi Tochigi, Japan|Boehringer Ingelheim Investigational Site 101, Toda Saitama, Japan|Boehringer Ingelheim Investigational Site 373, Tokushima Tokushima, Japan|Boehringer Ingelheim Investigational Site 374, Tokushima Tokushima, Japan|Boehringer Ingelheim Investigational Site 375, Tokushima Tokushima, Japan|Boehringer Ingelheim Investigational Site 6, Tomakomai Hokkaido, Japan|Boehringer Ingelheim Investigational Site 380, Toon Ehime, Japan|Boehringer Ingelheim Investigational Site 71, Toride Ibaraki, Japan|Boehringer Ingelheim Investigational Site 220, Toyama Toyama, Japan|Boehringer Ingelheim Investigational Site 221, Toyama Toyama, Japan|Boehringer Ingelheim Investigational Site 263, Toyohashi Aichi, Japan|Boehringer Ingelheim Investigational Site 308, Toyonaka Osaka, Japan|Boehringer Ingelheim Investigational Site 273, Toyota Aichi, Japan|Boehringer Ingelheim Investigational Site 279, Tsu Mie, Japan|Boehringer Ingelheim Investigational Site 66, Tsuchiura Ibaraki, Japan|Boehringer Ingelheim Investigational Site 67, Tsuchiura Ibaraki, Japan|Boehringer Ingelheim Investigational Site 68, Tsuchiura Ibaraki, Japan|Boehringer Ingelheim Investigational Site 69, Tsukuba Ibaraki, Japan|Boehringer Ingelheim Investigational Site 72, Tsukuba Ibaraki, Japan|Boehringer Ingelheim Investigational Site 55, Tsuruoka Yamagata, Japan|Boehringer Ingelheim Investigational Site 354, Tsuyama Okayama, Japan|Boehringer Ingelheim Investigational Site 370, Ube Yamaguchi, Japan|Boehringer Ingelheim Investigational Site 240, Ueda Nagano, Japan|Boehringer Ingelheim Investigational Site 290, Uji Kyoto, Japan|Boehringer Ingelheim Investigational Site 431, Urasoe Okinawa, Japan|Boehringer Ingelheim Investigational Site 404, Ureshino Saga, Japan|Boehringer Ingelheim Investigational Site 81, Utsunomiya Tochigi, Japan|Boehringer Ingelheim Investigational Site 82, Utsunomiya Tochigi, Japan|Boehringer Ingelheim Investigational Site 344, Wakayama Wakayama, Japan|Boehringer Ingelheim Investigational Site 412, Yamaga Kumamoto, Japan|Boehringer Ingelheim Investigational Site 49, Yamagata Yamagata, Japan|Boehringer Ingelheim Investigational Site 50, Yamagata Yamagata, Japan|Boehringer Ingelheim Investigational Site 51, Yamagata Yamagata, Japan|Boehringer Ingelheim Investigational Site 52, Yamagata Yamagata, Japan|Boehringer Ingelheim Investigational Site 197, Yamato Kanagawa, Japan|Boehringer Ingelheim Investigational Site 401, Yanagawa Fukuoka, Japan|Boehringer Ingelheim Investigational Site 319, Yao Osaka, Japan|Boehringer Ingelheim Investigational Site 320, Yao Osaka, Japan|Boehringer Ingelheim Investigational Site 276, Yokkaichi Mie, Japan|Boehringer Ingelheim Investigational Site 277, Yokkaichi Mie, Japan|Boehringer Ingelheim Investigational Site 187, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 188, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 189, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 190, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 191, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 194, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 195, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 196, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 199, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 200, Yokohama Kanagawa, Japan|Boehringer Ingelheim Investigational Site 192, Yokosuka Kanagawa, Japan|Boehringer Ingelheim Investigational Site 193, Yokosuka Kanagawa, Japan|Boehringer Ingelheim Investigational Site 345, Yonago Tottori, Japan|Boehringer Ingelheim Investigational Site 229, Yoshida Fukui, Japan|Boehringer Ingelheim Investigational Site 230, Yoshida Fukui, Japan|Boehringer Ingelheim Investigational Site 400, Yukuhashi Fukuoka, Japan Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.39mL

0.28mL

0.14mL

6.96mL

1.39mL

0.70mL

13.93mL

2.79mL

1.39mL

References

 

Historical Records

Categories