Structure of BMS-754807
CAS No.: 1001350-96-4
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Target |
|
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 << |
Tags: BMS-754807 | BMS754807 | BMS 754807 | IGF-1R | Insulin Receptor | Insulin-like growth factor-1 receptor | 1001350-96-4
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