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Chemical Structure| 649735-63-7 Chemical Structure| 649735-63-7

Structure of Brivanib (alaninate)
CAS No.: 649735-63-7

Chemical Structure| 649735-63-7

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Brivanib alaninate (BMS-582664) is an ATP-competitive VEGFR2 inhibitor with an IC50 of 25 nM; it moderately inhibits VEGFR1 and FGFR1, with selectivity for VEGFR2 over PDGFRβ by 240-fold.

Synonyms: Brivanib alaninate; BMS-582664

4.5 *For Research Use Only !

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Product Details of Brivanib (alaninate)

CAS No. :649735-63-7
Formula : C22H24FN5O4
M.W : 441.46
SMILES Code : C[C@@H](C(O[C@@H](COC1=CN2N=CN=C(C2=C1C)OC3=C(C4=C(C=C3)NC(C)=C4)F)C)=O)N
Synonyms :
Brivanib alaninate; BMS-582664
MDL No. :MFCD22577162
InChI Key :LTEJRLHKIYCEOX-OCCSQVGLSA-N
Pubchem ID :11154925

Safety of Brivanib (alaninate)

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H360
Precautionary Statements:P201-P308+P313
Class:6.1
UN#:2811
Packing Group:

Related Pathways of Brivanib (alaninate)

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HepG2 cells 60 μM 72 hours Evaluate the effect of SR9009 on BMAL1 mRNA expression PMC6461893
TFK1 cells 60 μM 72 hours To evaluate the effect of Notch3 silencing on Brivanib sensitivity, results showed that Notch3 silencing enhanced Brivanib-induced apoptosis. PMC6461893
MCF7 cells 60 μM 72 hours To evaluate the effect of IKBKE overexpression on cell invasion and migration, results showed that IKBKE overexpression significantly enhanced cell invasion and migration. PMC6461893
UWB1.289+BRCA1 cells 0, 8, 40, 200 μM 24 hours Evaluate the anti-proliferative effect of Brivanib on UWB1.289+BRCA1 cells, results showed IC50 value of Brivanib was 118.1 μM PMC10647199
UWB1.289 cells 0, 8, 40, 200 μM 24 hours Evaluate the anti-proliferative effect of Brivanib on UWB1.289 cells, results showed IC50 value of Brivanib was 170.2 μM PMC10647199
PEO1 cells 0, 8, 40, 200 μM 24 hours Evaluate the anti-proliferative effect of Brivanib on PEO1 cells, results showed IC50 value of Brivanib was 41.54 μM PMC10647199
Human umbilical vein endothelial cells (HUVECs) 300 nM and 900 nM 14 days To evaluate the effect of R-2-HG on endothelial cell migration, results showed that R-2-HG significantly enhanced the migration ability of HUVECs. PMC9234334
Hep3B cells 60 μM 72 hours BMP9 promotes cell cycle progression by reducing RNA m6A methylation levels PMC6461893
Huh7 cells 60 μM 72 hours PMC6461893

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Wistar rats DENA-induced HCC model Oral gavage 60 mg/kg Once daily for 15 consecutive days To evaluate the inhibitory effect of Notch3 silencing combined with Brivanib treatment on HCC tumor growth, results showed that the combination significantly inhibited tumor growth. PMC6461893
BALB/c athymic mice MCF-7 E2 tumors Oral 0.05 mg/g and 0.1 mg/g Daily administration for 6 weeks Brivanib alaninate significantly inhibited tumor growth in SERM sensitive and SERM stimulated models. The high dose (0.1 mg/g) significantly reduced tumor growth (p=0.001), while the low dose (0.05 mg/g) showed no significant effect. PMC2927957
Mice Pancreatic neuroendocrine tumors (PNET) model Oral 75 mg/kg Once daily until endpoint Evaluate the efficacy of Brivanib as first and second-line therapy in PNET model, showing significant survival benefit and tumor growth inhibition PMC3156934
BALB/c nu/nu mice PEO1 xenograft model Oral gavage 100mg/kg Once daily for 6 days Evaluate the inhibitory effect of Brivanib combined with Niraparib on PEO1 xenografts, results showed significant tumor growth inhibition PMC10647199

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00594984 Metastatic Colorectal Cancer (... More >>MCRC) Less << Phase 1 Phase 2 Completed - United States, California ... More >> Usc/Norris Comprehensive Cancer Center Hospital Los Angeles, California, United States, 90033 Usc/Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033 United States, Kentucky James Graham Brown Cancer Center Louisville, Kentucky, United States, 40202 United States, Missouri Washington University Saint Louis, Missouri, United States, 63110 Argentina Local Institution Buenos Aires, Argentina, C1426ANZ Denmark Local Institution Odense C, Denmark, 5000 Italy Local Institution Meldola Fc, Italy, 47014 Local Institution Milano, Italy, 20141 Korea, Republic of Local Institution Seoul, Korea, Republic of, 135-710 Spain Local Institution Madrid, Spain, 28050 Sweden Local Institution Stockholm, Sweden, 17176 Local Institution Uppsala, Sweden, 75185 Less <<
NCT00300027 Gastrointestinal Neoplasms PHASE1 TERMINATED - Local Institution, Little Rock... More >>, Arkansas, United States|Local Institution, Los Angeles, California, United States|Local Institution, Washington, District of Columbia, United States|Local Institution, Iowa City, Iowa, United States|Local Institution, Durham, North Carolina, United States|Local Institution, Temple, Texas, United States Less <<
NCT00207103 Tumors Neopla... More >>sm Metastasis Less << Phase 1 Completed - United States, California ... More >> Premiere Oncology Santa Monica, California, United States, 90404 United States, Indiana Indiana University Med Center Indianapolis, Indiana, United States, 46202 United States, Wisconsin University Of Wisconsin Comprehensive Center Madison, Wisconsin, United States, 53792 Canada, Alberta Local Institution Edmonton, Alberta, Canada, T6G 1Z2 Canada, Ontario Local Institution Ottawa, Ontario, Canada, K1H 1C4 Italy Local Institution Milano, Italy, 20141 United Kingdom Local Institution Middlesex, Greater London, United Kingdom, HA6 2RN Local Institution Manchester, Greater Manchester, United Kingdom, M20 4BX Less <<
NCT01046864 Gastro-Intestinal Cancer Phase 1 Completed - United States, California ... More >> Usc/Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033 United States, Texas Texas Oncology Dallas, Texas, United States, 75246 Scott & White Memorial Hospital And Clinic Temple, Texas, United States, 76508 Canada, Alberta Local Institution Edmonton, Alberta, Canada, T6G 1Z2 Canada, Ontario Local Institution Ottawa, Ontario, Canada, K1H 8L6 France Local Institution Villejuif Cedex, France, 94800 Less <<
NCT00207051 Colorectal Cancer Phase 1 Completed - United States, California ... More >> Usc/Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033 United States, District of Columbia Georgetn Univ Lombardi Can Ctr Washington, District of Columbia, United States, 20007 United States, Florida University Of Miami Miller School Of Medicine Miami, Florida, United States, 33010 H. Lee Moffitt Cancer Center Tampa, Florida, United States, 33612 United States, Michigan Karmanos Cancer Institute Detroit, Michigan, United States, 48201 Canada, Ontario Local Institution Hamilton, Ontario, Canada, L8V 2C5 Local Institution Toronto, Ontario, Canada, M5G 2M9 Netherlands Local Institution Amsterdam, Netherlands, 1081 HV Less <<
NCT00858871 Hepato Cellular Carcinoma (HCC... More >>) Less << Phase 3 Completed - -
NCT01253668 Renal Cell Carcinoma Phase 2 Completed - United States, Pennsylvania ... More >> Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104 Less <<
NCT00640471 Colorectal Cancer Phase 3 Completed - -
NCT00633789 Advanced Non-small Cell Lung C... More >>ancer Transitional Cell Carcinoma Soft Tissue Sarcoma Gastric/Esophageal Adenocarcinoma Pancreatic Cancer Including Ampulla of Vater Less << Phase 2 Completed - -
NCT00390936 Solid Tumors Phase 1 Completed - Japan ... More >> Local Institution Sunto-Gun, Shizuoka, Japan, 411-8777 Less <<
NCT01367275 Colorectal Cancer ... More >> Colorectal Adenocarcinoma Less << Phase 2 Terminated(Sponsor closed stud... More >>y) Less << - United States, Texas ... More >> UT MD Anderson Cancer Center Houston, Texas, United States, 77030 Less <<
NCT00825955 Liver Cancer Phase 3 Terminated(Efficacy endpoint m... More >>et, however, overall experimental dosing regimen is not considered optimal to support further clinical development in this patient population) Less << - -
NCT00908752 Hepatocellular Carcinoma Phase 3 Completed - -
NCT00435669 Tumors Phase 1 Completed - United States, Ohio ... More >> Cleveland Clinic Foundation Cleveland, Ohio, United States, 44195 Less <<
NCT00798252 Advanced Cancer Phase 1 Completed - United States, California ... More >> Usc/Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033 United States, Massachusetts Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215 United States, Michigan Wayne State University Detroit, Michigan, United States, 48201 Canada, Alberta Local Institution Edmonton, Alberta, Canada, T6G 1Z2 Canada, Ontario Local Institution Toronto, Ontario, Canada, M5G 2M9 Less <<
NCT00437424 Carcinoma, Hepatocellular Phase 1 Completed - United States, Alabama ... More >> University Of Alabama At Birmingham Birmingham, Alabama, United States, 35294 United States, California Usc/Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033 United States, Ohio Case Western Reserve University Clleveland, Ohio, United States, 44106 United States, Texas South Texas Accelerated Research Therapeutics, Llc San Antonio, Texas, United States, 78229 Spain Local Institution Sevilla, Spain, 41013 Less <<
NCT00888173 Endometrial Adenocarcinoma ... More >> Endometrial Clear Cell Adenocarcinoma Endometrial Mixed Adenocarcinoma Endometrial Mucinous Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Squamous Cell Carcinoma Endometrial Transitional Cell Carcinoma Endometrial Undifferentiated Carcinoma Recurrent Uterine Corpus Carcinoma Less << Phase 2 Completed - -
NCT03516071 Hepatocellular Carcinoma (HCC) Phase 2 Recruiting May 10, 2019 China, Anhui ... More >> Anhui Provincial Hospital Recruiting Hefei, Anhui, China Contact: Yueyin Pan          China, Guangdong Nanfang Hospital Recruiting Guangzhou, Guangdong, China Contact: Jinlin Hou          Sun Yat-sen University Cancer Center Recruiting Guangzhou, Guangdong, China Contact: Li Xu          China, Heilongjiang Harbin Medical University Cancer Hospital Recruiting Harbin, Heilongjiang, China Contact: Yuxian Bai          China, Henan Henan Cancer Hospital Recruiting Zhengzhou, Henan, China Contact: Xinfang Hou          China, Hunan Hunan Cancer Hospital Recruiting Changsha, Hunan, China Contact: Shanzhi Gu          China, Jiangsu China PLA 81st hospital Recruiting Nanjing, Jiangsu, China Contact: Shukui Qin          China, Jilin The first Hospital of Jilin University Recruiting Changchun, Jilin, China Contact: Wei Li          China, Liaoning Army General Hospital of Shenyang military region Recruiting Shenyang, Liaoning, China Contact: Zhendong Zheng          China, Shanghai Fudan University Shanghai Cancer Center Recruiting Shanghai, Shanghai, China Contact: Zhiqiang Meng          Zhongshan Hospital Recruiting Shanghai, Shanghai, China Contact: Zhenggang Ren          China, Shanxi Tangdu Hospital Recruiting Xi'an, Shanxi, China Contact: Helong Zhang          China, Sichuan West China Hospital West China School of Medicine Sichuan University Recruiting Chengdu, Sichuan, China Contact: Hong Zhu          China, Tianjin Tianjin Medical University Cancer Institute & Hospital Recruiting Tianjin, Tianjin, China Contact: Tianqiang Song          China, Zhejiang Zhejiang Cancer Hospital Recruiting Hangzhou, Zhejiang, China Contact: Jieer Ying Less <<
NCT01108705 Carcinoma, Hepatocellular Phase 3 Terminated - -
NCT00888173 - Completed - -
NCT00355238 Hepatocellular Carcinoma (HCC) Phase 2 Completed - -
NCT01267253 - Active, not recruiting - -
NCT01540461 Hepatocellular Carcinoma Phase 1 Completed - China, Beijing ... More >> Local Institution Beijing, Beijing, China, 100071 China, Heilongjiang Local Institution Ha Erbin, Heilongjiang, China, 150040 China, Jiangsu Local Institution Nanjing, Jiangsu, China, 210002 Less <<
NCT01267253 Cervical Adenocarcinoma ... More >> Cervical Adenosquamous Carcinoma Cervical Squamous Cell Carcinoma, Not Otherwise Specified Persistent Disease Recurrent Cervical Carcinoma Less << Phase 2 Active, not recruiting - -
NCT00437437 Tumors Phase 1 Completed - United States, Massachusetts ... More >> Dana-Farber Harvard Cancer Care Boston, Massachusetts, United States, 02115 United States, Michigan Wayne State University Detroit, Michigan, United States, 48201-2194 United States, North Carolina Duke University Medical Center-Dept Of Medicine Durham, North Carolina, United States, 27710 Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.27mL

0.45mL

0.23mL

11.33mL

2.27mL

1.13mL

22.65mL

4.53mL

2.27mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

Historical Records

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