1. Neuronal Signaling
    Stem Cell/Wnt
  2. γ-secretase
  3. BMS-906024


目录号: HY-15670

BMS-906024 是一种口服有效,选择性的 γ 分泌酶 (γ-secretase; gamma secretase) 抑制剂。BMS-906024 是有效的,泛 Notch 受体抑制剂,对 Notch1,-2,-3 和 -4 受体的 IC50 值分别为 1.6 nM,0.7 nM,3.4 nM 和 2.9 nM。BMS-906024 表现广谱抗肿瘤活性。

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BMS-906024 Chemical Structure

BMS-906024 Chemical Structure

CAS No. : 1401066-79-2

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BMS-906024 is an orally active and selective γ-secretase (gamma secretase) inhibitor. BMS-906024 is a potent pan-Notch receptors inhibitor with IC50s of 1.6 nM, 0.7 nM, 3.4 nM, and 2.9 nM for Notch1, -2, -3, and -4 receptors, respectively. BMS-906024 demonstrates broad-spectrum antineoplastic activity[1][2].

IC50 & Target

IC50: 1.6 nM (Notch1), 0.7 nM (Notch2), 3.4 nM (Notch3) and 2.9 nM (Notch4)[2]

In Vitro

BMS-906024 (5-100 nM; 72 hours) reduces Notch1 ICD levels in all six lung cancer cell lines. BMS-906024 at 100 nM, has no effect on total Notch1, and down-regulated Hes1 transcript[1].
In cancer cell proliferation assays, BMS-906024 inhibits both leukemia (TALL-1) and triple-negative breast cancer (MDA-MB-468) cells with IC50 of ∼4 nM[2].
BMS-906024 (100 nM; for 72 hours) enhances the anti-tumor activity of Paclitaxel in vitro[1].

Western Blot Analysis[1]

Cell Line: NSCLC cell lines (A549, H358, H1975, H2444, H1792, HCC44)
Concentration: 5, 10, 25, 50, 100 nM
Incubation Time: 72 hours
Result: Reduced Notch1 ICD levels in all six lung cancer cell lines tested at concentrations as low as 5 nM, with maximal depletion at 50-100 nM.
In Vivo

BMS-906024 (8.5 mg/kg; oral gavage; days 1 through 4 of each week for 3 weeks) significantly enhances the tumor growth inhibition of Paclitaxel (36 mg/kg). BMS-906024 enhances Paclitaxel-mediated cytotoxicity in vivo in NSCLC through a combination of inhibiting proliferation and promoting apoptosis, in a p21 and p57-independent manner[1].
BMS-906024 has a T1/2 of 4.6/5.3 hours, a Cmax of 1/0.3 μM and an AUC of 3.4/1.9 μM•hour for IV/PO[2].

Animal Model: Six to 12-week-old female NOD scid gamma (NSG) mice with KRAS- and BRAF-WT PDX-T42 xenografts[1]
Dosage: 8.5 mg/kg
Administration: oral gavage; days 1 through 4 of each week for 3 weeks
Result: Significantly enhanced the tumor growth inhibition of Paclitaxel (36 mg/kg), but had no significant effect on Cisplatin (2 mg/kg) treatment.
Animal Model: Mouse[2]
Dosage: 1 mg/kg (Pharmacokinetic Analysis)
Administration: IV or PO
Result: Had a T1/2 of 4.6/5.3 hours, a Cmax of 1/0.3 μM and an AUC of 3.4/1.9 μM•hour for IV/PO.
Clinical Trial
Molecular Weight









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BMS-906024BMS906024BMS 906024γ-secretaseNotchGamma secretaseoralNotch1Notch2Notch3Notch4broad-spectrumantineoplasticInhibitorinhibitorinhibit


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