| Identification | Back Directory | [Name]
Benzamide, 2-[(trans-4-hydroxycyclohexyl)amino]-4-(4,5,6,7-tetrahydro-3,6,6-trimethyl-4-oxo-1H-indazol-1-yl)- | [CAS]
908112-37-8 | [Synonyms]
AT-533
Benzamide, 2-[(trans-4-hydroxycyclohexyl)amino]-4-(4,5,6,7-tetrahydro-3,6,6-trimethyl-4-oxo-1H-indazol-1-yl)- | [Molecular Formula]
C23H30N4O3 | [MOL File]
908112-37-8.mol | [Molecular Weight]
410.51 |
| Chemical Properties | Back Directory | [Melting point ]
133.8-136.1 °C | [Boiling point ]
631.0±55.0 °C(Predicted) | [density ]
1.36±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
15.09±0.40(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3]. | [in vivo]
AT-533 (10 mg/kg; i.p.; once daily for 21 d) suppresses the expression of the HIF-1α/VEGF signaling pathway-related proteins in MDA-MB-231 breast cancer xenografts tumor model in mouse[1].
AT-533 (1, 2 and 4 mg/kg; i.p.; once daily for 30 d) has no mortality, loss of appetite and body weight, adverse reactions in Sprague-Dawley rats in subacute toxicity test[3]. | Animal Model: | Male C57BL/6 mice with MDA-MB-231 breast cancer xenografts[1] | | Dosage: | 10 mg/kg; | | Administration: | Intraperitoneal injection; once daily for 21 days | | Result: | Significantly downregulated HIF-1α and VEGF expression. |
| [IC 50]
HSP90; HSV-1; ERK1; ERK2; NF-κB; Akt; HIF-1α; VEGF/VEGFR-2 | [References]
[1] Zhang PC, et al. AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and HIF-1α/VEGF/VEGFR-2-mediated angiogenesis in vitro and in vivo. Biochem Pharmacol. 2020 Feb;172:113771. DOI:10.1016/j.bcp.2019.113771
[2] Li F, et al. AT-533, a Hsp90 inhibitor, attenuates HSV-1-induced inflammation. Biochem Pharmacol. 2019 Aug;166:82-92. DOI:10.1016/j.bcp.2019.05.003
[3] Wu Y, et al. Subacute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats. Exp Ther Med. 2021 Jun;21(6):632. DOI:10.3892/etm.2021.10064 |
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