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Chemical Structure| 854001-07-3 Chemical Structure| 854001-07-3

Structure of Dasatinib HCl
CAS No.: 854001-07-3

Chemical Structure| 854001-07-3

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Dasatinib (BMS-354825) hydrochloride is a highly potent, ATP-competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity, having Kis of 16 pM and 30 pM for Src and Bcr-Abl, respectively. It inhibits Bcr-Abl and Src with IC50 values of <1.0 nM and 0.5 nM, respectively, and induces apoptosis and autophagy.

Synonyms: BMS-354825 hydrochloride; Dasatinib hydrochloride; BMS-354825 HCl

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Product Details of Dasatinib HCl

CAS No. :854001-07-3
Formula : C22H27Cl2N7O2S
M.W : 524.47
SMILES Code : O=C(C1=CN=C(S1)NC2=NC(C)=NC(N3CCN(CC3)CCO)=C2)NC4=C(C=CC=C4Cl)C.[H]Cl
Synonyms :
BMS-354825 hydrochloride; Dasatinib hydrochloride; BMS-354825 HCl
MDL No. :MFCD26960525
InChI Key :MSCGWICDJYLQOJ-UHFFFAOYSA-N
Pubchem ID :11466607

Safety of Dasatinib HCl

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

Related Pathways of Dasatinib HCl

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
SUM229 25 nM 24 and 72 h Inhibit nEGFR translocation and enhance non-nuclear EGFR levels Mol Cancer Ther. 2014 May;13(5):1356-68.
SUM149 25 nM 24 and 72 h Inhibit nEGFR translocation and enhance non-nuclear EGFR levels Mol Cancer Ther. 2014 May;13(5):1356-68.
SU-DHL-8 cells 100 nM 24 h To assess the inhibitory effect of dasatinib on CD19-TCB-mediated target-cell killing. Results showed that 100 nM dasatinib significantly inhibited target-cell killing. J Immunother Cancer. 2021 Jul;9(7):e002582.
MDAMB468 25 nM 24 and 72 h Inhibit nEGFR translocation and enhance non-nuclear EGFR levels Mol Cancer Ther. 2014 May;13(5):1356-68.
MKN45 cells 100 nM 3 days To assess the inhibitory effect of dasatinib on CEA-TCB-mediated target-cell killing. Results showed that 100 nM dasatinib significantly inhibited target-cell killing. J Immunother Cancer. 2021 Jul;9(7):e002582.
A375 cells 100 nM 24 h To assess the inhibitory effect of dasatinib on HLA-A2 WT1-TCB-mediated target-cell killing. Results showed that 100 nM dasatinib significantly inhibited target-cell killing. J Immunother Cancer. 2021 Jul;9(7):e002582.
SKM-1 cells 50 nM 24 h To assess the inhibitory effect of dasatinib on HLA-A2 WT1-TCB-mediated target-cell killing. Results showed that 50 nM dasatinib significantly inhibited target-cell killing. J Immunother Cancer. 2021 Jul;9(7):e002582.
REH GCR cells 100-300 nM 48 h Dasatinib combined with dexamethasone increased apoptosis, with Bliss synergy analysis showing additive effects (mean synergy score: 8.8). Nat Commun. 2023 May 22;14(1):2935.
NALM6 cells 100-300 nM 48 h Dasatinib combined with dexamethasone significantly increased apoptosis, with Bliss synergy analysis showing high synergy (mean synergy score: 30.8). Nat Commun. 2023 May 22;14(1):2935.
PS125 cells 3nM or 10nM 24 h Dasatinib alone at 3nM had no effect on PS125 cell viability, but showed synergistic effect when combined with AT9283. Cancer Lett. 2014 Nov 1;354(1):68-76.
D556 cells 1, 5, 10, 50 and 100nM 1-24 h Dasatinib markedly decreased p-Src levels, with near ablation of detectable p-Src following treatment with 5 and 10nM. Cancer Lett. 2014 Nov 1;354(1):68-76.
DAOY cells 1, 5, 10, 50 and 100nM 1-24 h Dasatinib markedly decreased p-Src levels, with near ablation of detectable p-Src following treatment with 5 and 10nM. Cancer Lett. 2014 Nov 1;354(1):68-76.
human K562 cells 5 nM 48 h Evaluate the effect of Dasatinib on cell viability, results showed Dasatinib fully suppressed cell growth Nat Med. 2010 Feb;16(2):205-13.
human SUP-B15 cells 5 nM 48 h Evaluate the effect of Dasatinib on cell viability, results showed Dasatinib fully suppressed cell growth Nat Med. 2010 Feb;16(2):205-13.
mouse p190 BCR-ABL transformed hematopoietic progenitors 5 nM 48 h Evaluate the effect of Dasatinib on cell viability, results showed Dasatinib fully suppressed cell growth Nat Med. 2010 Feb;16(2):205-13.
human bone marrow-derived mesenchymal stem cells (BM-MSCs) 1 μM 21 days To evaluate the effect of Dasatinib on adipogenesis in BM-MSCs. Results showed that Dasatinib reduced adipogenesis, decreasing the number and proportion of ORO-positive cells. Cardiovasc Diabetol. 2023 Aug 17;22(1):214.
RL-95 cells 100 nM 48 h Evaluate the effect of Dasatinib on p-p44/42 MAPK Gynecol Oncol. 2021 Oct;163(1):181-190.
KG-1 cells 100 nM Inhibit Src kinase activity and reduce cell proliferation Cancer Res. 2011 Dec 1;71(23):7312-22.
BaF3 cells 10 nM and 100 nM 72 h Inhibit Src kinase activity and reduce cell proliferation Cancer Res. 2011 Dec 1;71(23):7312-22.
Ishikawa cells 100 nM 48 h Evaluate the effect of Dasatinib on p-p44/42 MAPK, results showed slight induction of pMAPK Gynecol Oncol. 2021 Oct;163(1):181-190.
HEC-1A cells 100 nM 48 h Evaluate the effect of Dasatinib on p-p44/42 MAPK, results showed slight induction of pMAPK Gynecol Oncol. 2021 Oct;163(1):181-190.
Normal CD34+ progenitors 10nM Combined with JAK2 inhibitor to inhibit self-renewal potential Cell Stem Cell. 2016 Aug 4;19(2):177-191.
K562 leukemia cells 10nM Inhibited BCR-ABL1 signaling and reduced leukemia stem cell self-renewal potential Cell Stem Cell. 2016 Aug 4;19(2):177-191.
Human umbilical vein endothelial cells (HUVEC) 10 nM 30 min Dasatinib markedly inhibited HUVEC response to exosomes Angiogenesis. 2012 Mar;15(1):33-45.
K562 chronic myeloid leukemia cells 0.1 nM 24 or 48 h Dasatinib reduced the total exosome release from K562 cells Angiogenesis. 2012 Mar;15(1):33-45.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Humanized NSG mice Humanized NSG mouse model Oral 50 mg/kg Three times on day 0 and twice on days 1 and 2 To assess the inhibitory effect of dasatinib on CD19-TCB-mediated B cell depletion and cytokine release. Results showed that 50 mg/kg dasatinib significantly inhibited B cell depletion and cytokine release. J Immunother Cancer. 2021 Jul;9(7):e002582.
C7BL/6 mice Mouse flank syngeneic MB tumor model Oral gavage 15 mg/kg/day Once daily for 5 consecutive days per week for 4 weeks Dasatinib treatment resulted in significant reduction in MB tumor volume, with significantly lower tumor volumes compared to controls after 20 days of treatment. Cancer Lett. 2014 Nov 1;354(1):68-76.
Mice SUP-B15-luciferase xenograft model Oral 2.5 mg/kg Daily doses throughout the full treatment duration Evaluate the effect of Dasatinib alone or in combination with PP242 on leukemic cell expansion, results showed combination treatment caused regression of leukemic disease Nat Med. 2010 Feb;16(2):205-13.
Mice (BKS.Cg-+Leprdb/+Leprdb/OlaHsd (db/db)) Obese type 2 diabetes model Oral gavage 5 mg/kg Once per week for four weeks To assess the effect of Dasatinib on cardiac lipid deposition and function. Results showed that Dasatinib reduced lipid accumulation in the heart and bone marrow, improved diastolic function indices (E/A ratio and non-flow time), and decreased cardiac fibrosis and expression of the senescence marker p16. Cardiovasc Diabetol. 2023 Aug 17;22(1):214.
Nude mice HEC-1A orthotopic model Oral 15 mg/kg Daily until the end of the experiment Evaluate the antitumor effect of Dasatinib alone or in combination with Trametinib, results showed that combination treatment significantly enhanced antitumor response Gynecol Oncol. 2021 Oct;163(1):181-190.
RAG2−/−γc−/− mice Humanized BC CML mouse model Oral gavage 50 mg/kg Daily for two weeks Inhibited BC LSC survival and self-renewal, prolonged survival of serially transplanted mice Cell Stem Cell. 2016 Aug 4;19(2):177-191.
BALB/c nude mice Matrigel plug model Oral 20 mg/kg Once daily for 14 days Dasatinib abrogated K562 exosome-induced angiogenesis Angiogenesis. 2012 Mar;15(1):33-45.
Balb/c mice ZNF112 and CEP2A cell transplantation model Oral 20 mg/kg and 40 mg/kg 6 days per week for 4 weeks Inhibit Src kinase activity and prolong survival Cancer Res. 2011 Dec 1;71(23):7312-22.
Athymic nude mice MDAMB468 xenograft model Oral gavage 50 mg/kg Once daily for 4 days Inhibit nEGFR translocation and enhance membrane EGFR accumulation Mol Cancer Ther. 2014 May;13(5):1356-68.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.91mL

0.38mL

0.19mL

9.53mL

1.91mL

0.95mL

19.07mL

3.81mL

1.91mL

References

[1]Shah NP, Lee FY, et al. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood. 2006 Jul 1;108(1):286-91.

[2]O'Hare T, Walters DK, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5.

[3]Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001 Apr 5;344(14):1038-42. doi: 10.1056/NEJM200104053441402. Erratum in: N Engl J Med 2001 Jul 19;345(3):232. PMID: 11287973.

[4]O'Hare T, Walters DK, Stoffregen EP, Jia T, Manley PW, Mestan J, Cowan-Jacob SW, Lee FY, Heinrich MC, Deininger MW, Druker BJ. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5. doi: 10.1158/0008-5472.CAN-05-0259. PMID: 15930265.

[5]Chan CM, Jing X, Pike LA, Zhou Q, Lim DJ, Sams SB, Lund GS, Sharma V, Haugen BR, Schweppe RE. Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis. Clin Cancer Res. 2012 Jul 1;18(13):3580-91. doi: 10.1158/1078-0432.CCR-11-3359. Epub 2012 May 14. PMID: 22586301; PMCID: PMC3931551.

 

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