Birinapant

Research use only, not for human use.

Birinapant is a SMAC mimetic antagonist, mostly to cIAP1 with Kd of <1 nM, less potent to XIAP. Phase 2.

Birinapant is a SMAC mimetic antagonist, mostly to cIAP1 with Kd of <1 nM, less potent to XIAP. Phase 2.(In Vitro):Birinapant (TL32711) (30-10000 nM; 24 hours) significantly decreases the viability of SUM190 cells in a dose-dependent manner.Birinapant (TL32711) (30-1000 nM; 4 hours) shows a significant decrease in cIAP1 levels and enhanced PARP cleavage, and induces apoptosis.Birinapant (TL32711) binds with high affinity to the isolated BIR3 domains of cIAP1, cIAP2, and XIAP and the single BIR domain of ML-IAP and rapidly degrades TRAF2-bound cIAP1 and cIAP2 thereby inhibiting TNF-mediated NF-κB activation.(In Vivo):Birinapant (TL32711) (30 mg/kg; i.p.; every third day (*5)) shows antitumor efficacy and are devoid of overt toxicity in preclinical models.

Cell Viability Assay Cell Line:TRAIL-resistant SUM190 IBC cells Concentration:30, 100, 300, 1000, 10000 nM Incubation Time:24 hours Result:Significantly decreased the viability of SUM190 cells in a dose-dependent manner.Western Blot Analysis Cell Line:SUM190 cells Concentration:30, 300, 1000 nM Incubation Time:4 hours Result:Showed a significant decrease in cIAP1 levels and enhanced PARP cleavage.

Animal Model:Female athymic nude mice (low-passage, patient-derived xenotransplant models of ovarian cancer, colorectal cancer, and melanoma)Dosage:30 mg/kg Administration:Intraperitoneal injection; every third day (*5)Result:Resulted in inhibition of tumor growth.

TL-32711

Apoptosis

IAP

cIAP1| XIAP

Cancer

——

1260251-31-7

806.94

C42H56F2N8O6

>98% (HPLC)

DMSO:100 mg/mL (123.92 mM); Ethanol:55 mg/mL (68.15 mM); Water：<1 mg/mL (<1 mM)

C[C@H](NC)C(N[C@@H](CC)C(N1[C@H](CC2=C(C(N3)=C(C[C@H]4N(C([C@@H](NC([C@@H](NC)C)=O)CC)=O)C[C@@H](O)C4)C5=C3C=C(F)C=C5)NC6=C2C=CC(F)=C6)C[C@H](O)C1)=O)=O

(2S)-N-[(2S)-1-[(2R,4S)-2-[[6-fluoro-2-[6-fluoro-3-[[(2R,4S)-4-hydroxy-1-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]pyrrolidin-2-yl]methyl]-1H-indol-2-yl]-1H-indol-3-yl]methyl]-4-hydroxypyrrolidin-1-yl]-1-oxobutan-2-yl]-2-(methylamino)propanamide

(-20℃)

With Ice Pack

≥ 2 years