[CAS NO. 1570231-89-8] Dasminapant
PRODUCTS SPECIFICATIONS [1570231-89-8]
DESCRIPTION [1570231-89-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 1157.40 |
| Molecular Formula | C60H72N10O10S2 |
| SMILES | O=S(C1=CC=CC(S(=O)(N(C[C@@H]2NC([C@@H](NC)C)=O)CC[C@](CC[C@H]3C(NC(C4=CC=CC=C4)C5=CC=CC=C5)=O)([H])N3C2=O)=O)=C1)(N(C[C@@H]6NC([C@@H](NC)C)=O)CC[C@](CC[C@H]7C(NC(C8=CC=CC=C8)C9=CC=CC=C9)=O)([H])N7C6=O)=O |
Summary
APG-1387, a bivalent SMAC mimetic and an IAP antagonist, blocks the activity of IAPs family proteins (XIAP, cIAP-1 , cIAP-2 , and ML-IAP). APG-1387 induces degradation of cIAP-1 and XIAP proteins, as well as caspase-3 activation and PARP cleavage, which leads to apoptosis . APG-1387 can be used for the research of hepatocellular carcinoma, ovarian cancer , and nasopharyngeal carcinoma [1] [2] [3] [4] [5] .
IC50 & Target
IAP [1]
In Vitro
APG-1387 (0.02-20 μM; 24 h) induces rapid degradation of cIAPs in HepG2 and HCCLM3 cells
[1]
.
APG-1387 (2 μM; 24 h) enhances TNF-α- and TRAIL-mediated anti-cancer activities in HepG2 and HCCLM3 cells. APG-1387 sensitizes HepG2 and HCCLM3 cells to NK cell-mediated killing in vitro
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [1]
| Cell Line: | HepG2 and HCCLM3 cells |
| Concentration: | 0.02, 0.2, 2, 20 μM |
| Incubation Time: | 1, 6, 24 hours |
| Result: |
Decreased the expression of cIAP1 and cIAP2 in both cell lines in a dose- and time-dependent manner.
Inhibited the expression of X chromosome-linked IAP (XIAP) at a high dose. |
In Vivo
APG-1387 (20 mg/kg; i.p. every 3 days for 4 weeks) sensitizes HCCLM3 tumors toward NK cell-mediated killing in mice
[1]
.
APG-1387 (20 mg/kg; i.p. every 3 days for 4 weeks) monotherapy exhibits some degree of anti-tumor effect and is well tolerated in mice
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Non-obese diabetic and severe combined immunodeficiency (NOD-SCID) mice bearing HCCLM3 tumors are injected with NK cells [1] |
| Dosage: | 20 mg/kg |
| Administration: | I.p. every 3 days for 4 weeks |
| Result: |
Decreased the expression of cIAP1 and cIAP2, and less potent to XIAP expression.
Potentiated the effects of pre-activated NK cells on HCCLM3 xenograft tumor growth and tumor weight. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT04568265 | Ascentage Pharma Group Inc. |
Hepatitis B|Chronic Hep B|HBV
|
June 3, 2020 | Phase 2 |
| NCT03585322 | Ascentage Pharma Group Inc.|HealthQuest Pharma Inc. |
Chronic Hepatitis B
|
July 4, 2018 | Phase 1 |
| NCT03386526 | Ascentage Pharma Group Inc. |
Advanced Solid Tumors or Hematologic Malignancies
|
November 21, 2017 | Phase 1 |
| NCT04284488 | Ascentage Pharma Group Inc. |
Advanced Solid Tumor
|
April 10, 2020 | Phase 1|Phase 2 |
| NCT04643405 | Ascentage Pharma Group Inc. |
Advanced Pancreatic Cancer
|
March 17, 2021 | Phase 1|Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
DMSO : 50 mg/mL ( 43.20 mM ; Need ultrasonic)
H 2 O : < 0.1 mg/mL (insoluble)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 0.8640 mL | 4.3200 mL | 8.6401 mL |
| 5 mM | 0.1728 mL | 0.8640 mL | 1.7280 mL |
| 10 mM | 0.0864 mL | 0.4320 mL | 0.8640 mL |
References
- [1] Chen Z, et, al. The SMAC Mimetic APG-1387 Sensitizes Immune-Mediated Cell Apoptosis in Hepatocellular Carcinoma. Front Pharmacol. 2018 Nov 6; 9:1298.
- [2] Li BX, et, al. Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway. J Exp Clin Cancer Res. 2018 Mar 12;37(1):53.
- [3] Li N, et, al. A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis. Cancer Lett. 2016 Oct 10;381(1):14-22.
- [4] Li Q, et, al. Abstract 6216: Therapeutic potential of IAP inhibitor APG-1387 in combination with PARP- or MEK-targeted therapy, or chemotherapy in pancreatic cancer. American Association for Cancer Research. Aug 2020. 80(16).
- [5] Pan w, et, al. Abstract 1754: Smac mimetics APG-1387 synergizes with immune checkpoint inhibitors in preclinical models. American Association for Cancer Research. Jul 2018. 78(13).