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Chemical Structure| 1001350-96-4 Chemical Structure| 1001350-96-4

Structure of BMS-754807
CAS No.: 1001350-96-4

Chemical Structure| 1001350-96-4

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BMS-754807 is a potent and reversible inhibitor of IGF-1R/InsR with IC50 of 1.8 nM/1.7 nM, less potent to Met, Aurora A/B, TrkA/B and Ron, and shows little activity to Flt3, Lck, MK2, PKA, PKC etc.

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Product Details of BMS-754807

CAS No. :1001350-96-4
Formula : C23H24FN9O
M.W : 461.49
SMILES Code : O=C([C@@]1(C)N(C(N=C2NC3=NNC(C4CC4)=C3)=NN5C2=CC=C5)CCC1)NC6=CC=C(F)N=C6
MDL No. :MFCD18633202
InChI Key :LQVXSNNAFNGRAH-QHCPKHFHSA-N
Pubchem ID :24785538

Safety of BMS-754807

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

Related Pathways of BMS-754807

RTK
MAPK

Isoform Comparison

Biological Activity

Target
  • IGF-1R

    IGF-1R, IC50:1.8 nM

  • Insulin Receptor

    Insulin Receptor, IC50:1.7 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
HCT116 cells 240 nM 48-72 hours BMS-754807 treatment significantly induced p70S6K1 phosphorylation, indicating that IGF-1R inhibition activates p70S6K1 via MEK1/2 to promote cell survival PMC7447751
SW480 cells 240 nM 48-72 hours BMS-754807 treatment significantly induced p70S6K1 phosphorylation, indicating that IGF-1R inhibition activates p70S6K1 via MEK1/2 to promote cell survival PMC7447751
MCF-7/AC-1 cells 10 μmol/L 24 hours To evaluate the effect of BMS-754807 alone or in combination with hormonal therapies on the proliferation of MCF-7/AC-1 cells, results showed that BMS-754807 combined with 4-hydroxytamoxifen, letrozole, or fulvestrant had significant antiproliferative effects. PMC4004036
HCT116 cells 240 nM 48 and 72 hours Induced p70S6K1 phosphorylation, indicating activation of p70S6K1 through inhibition of IGF-1R signaling pathway PMC7447751
SW480 cells 240 nM 48 and 72 hours Induced p70S6K1 phosphorylation, indicating that this induction is independent of K-Ras or PIK3CA mutations PMC7447751
HT29-P cells 240 nM 24 to 72 hours Induced p70S6K1 phosphorylation, indicating that Pdcd4 knockdown enhanced BMS-754807-induced activation of p70S6K1, promoting cell survival PMC7447751
HCT116 cells 240 nM 72 hours Inhibition of p70S6K1 activation led to cell death, indicating that p70S6K1 phosphorylation is a key event for cell survival PMC7447751
Pa01C 200 nM 72 hours To evaluate the effect of BMS-754807 combined with CQ on PDAC cell proliferation, the results showed that the combination significantly increased cytotoxicity. PMC8886214
Pa14C 200 nM 72 hours To evaluate the effect of BMS-754807 combined with CQ on PDAC cell proliferation, the results showed that the combination significantly increased cytotoxicity. PMC8886214
mT4 200 nM 72 hours To evaluate the effect of BMS-754807 combined with CQ on PDAC cell proliferation, the results showed that the combination significantly increased cytotoxicity. PMC8886214
breast cancer cell lines 0.1 μM to 25 μM 72 hours To test the sensitivity of BMS-754807 in various breast cancer cell lines, results showed that triple-negative breast cancer cell lines were most sensitive to BMS-754807 PMC3073089
MIA-PaCa-2 cells 125 nM 72 hours The combination of BMS-754807 and PD-0332991 significantly inhibited the proliferation of MIA-PaCa-2 cells, showing a synergistic effect. PMC4122288
PSN1 cells 2.5-10 nM 2 hours and 16 hours The combination of BMS-754807 and PD-0332991 significantly inhibited the phosphorylation of S6K1 in PSN1 cells, showing a synergistic effect. PMC4122288
SMS-CTR 0 to 1000 nM 48 hours To assess the impact of trametinib and ganitumab on apoptosis, results showed that trametinib alone or in combination with ganitumab increased the apoptosis rate in SMS-CTR cells. PMC9852065
RD 0 to 1000 nM 48 hours To assess the impact of trametinib and ganitumab on apoptosis, results showed that trametinib alone or in combination with ganitumab increased the apoptosis rate in RD cells. PMC9852065

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice HCT116 cell xenograft model Intraperitoneal injection 100 mg/kg Once daily for 3 weeks The combination of BMS-754807 and U0126 significantly suppressed tumor growth, indicating that inhibition of MEK1/2 overcomes IGF-1R inhibition-induced p70S6K1 activation to promote cell death PMC7447751
nude mice MCF-7/AC-1 xenograft model oral 75 mg/kg Twice daily, continued until the end of the experiment To evaluate the antitumor activity of BMS-754807 alone or in combination with tamoxifen or letrozole in MCF-7/AC-1 xenografts, results showed that combination therapy significantly enhanced tumor regression without major side effects. PMC4004036
Nude mice HCT116 cell-derived tumor xenograft model Intraperitoneal injection 50 mg/kg/d once daily for 28 days Combination of BMS-754807 and U0126 significantly suppressed tumor growth, indicating that inhibition of MEK1/2 abolishes BMS-754807-induced p70S6K1 phosphorylation and promotes cell death PMC7447751
C57Bl/6 mice mT4 cell xenograft model Subcutaneous injection 25 mg/kg Once daily for 12 days To evaluate the effect of BMS-754807 combined with HCQ on tumor growth in the mT4 cell xenograft model, the results showed that the combination significantly reduced tumor burden. PMC8886214
mice triple-negative breast cancer tumorgraft model oral 10 mg/kg Once daily for 11 consecutive days To test the efficacy of BMS-754807 alone or in combination with chemotherapy in a triple-negative breast cancer tumorgraft model, results showed that BMS-754807 significantly inhibited tumor growth, and combination with chemotherapy led to complete tumor regression PMC3073089
Mice YAPC cell xenograft model Oral administration 12.5 mg/kg Daily until tumors reached 15 mm The combination of BMS-754807 and PD-0332991 significantly inhibited tumor growth in the YAPC cell xenograft model, showing a synergistic effect. PMC4122288
SCID beige mice RAS-mutated RMS xenograft models oral gavage and intraperitoneal injection 50mg/kg once daily for 14 days To evaluate the tumor growth inhibitory effect of trametinib and ganitumab combination therapy, results showed that the combination significantly inhibited tumor growth and prolonged survival in the SMS-CTR model. PMC9852065
Mice Whole-body 12-Gy γ-irradiation injury model Oral BMS-754807 15 mg/kg, PD-0332991 75 mg/kg Every other day for 21 days To investigate the role of IGF-1 signaling inhibition in intestinal regeneration after radiation injury. Results showed that BMS-754807-treated mice exhibited more pronounced post-irradiation weight loss and impaired intestinal regeneration, characterized by blunted villi, reduced proliferation, and a 20% decrease in regenerating crypts. PMC7502577

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00898716 Neoplasms PHASE1 COMPLETED 2025-07-11 Local Institution, Chuo-Ku, To... More >>kyo, 104-0045, Japan Less <<
NCT00569036 Neoplasms|Solid Tumors|Metasta... More >>ses Less << PHASE1 COMPLETED 2025-04-13 Local Institution, East Melbou... More >>rne, Victoria, 3002, Australia|Local Institution, Footscray, Victoria, 3011, Australia|Local Institution, Heidelberg, Victoria, 3084, Australia|Local Institution, Parkville, Victoria, 3050, Australia|Local Institution, Nedlands, Western Australia, 6009, Australia Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.17mL

0.43mL

0.22mL

10.83mL

2.17mL

1.08mL

21.67mL

4.33mL

2.17mL

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
 

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