Table 2.

Hsp90 inhibitors.

Class	HSP90 Inhibitor	Description	References
Natural products	Geldanamycin	Binds to the N-terminal ATP-binding site of HSP90, leading to client protein degradation and interference with cellular processes. Not suitable for clinical use due to toxicity, instability, and poor solubility.	[1]
	Radicicol	Binds to the ATP-binding site of HSP90, demonstrating potential as a multi-faceted approach to treating cancer.	[42]
Semisynthetic	17-AAG	Geldanamycin derivative that entered phase I clinical trials, but did not advance past phase II. Poor bioavailability.	[43,44]
	17-AAGH2	Improved the metabolic profile and potency of 17-AAG. Clinical trials were terminated or withdrawn.	[21]
	17-DMAG	Developed to improve the physiochemical profile of geldanamycin.	[45]
Purine-based	PU-3	First fully synthetic small-molecule HSP90 inhibitor; inhibits growth and differentiation in breast cancer cells.	[46]
	BIIB021 BIIB028 MPC-3100 PU-H71 Debio0932	Derivatives of the purine chemical scaffold in PU-3; entered clinical trials, but did not advance past phase II.	[47]
Benzamide	SNX-5422	Pyrazole-containing HSP90 inhibitor with promising bioavailability, but inhibits all HSP90 isoforms, leading to dose escalation challenges.	[48]
Resorcinol-containing	AUY922	Resorcinol-containing HSP90 inhibitor; active against tumor growth, angiogenesis, and metastasis.	[49]
	STA-9090	Modification of the resorcinol scaffold with a higher potency in downregulating oncoproteins and pathways. Advanced to phase III trials and is the most clinically evaluated HSP90 inhibitor.	[50]
	AT13387	Resorcinol-containing HSP90 inhibitor discovered by Astex Therapeutics, with a high potency and ideal ligand efficacy.	[51]
	KW-2478	Discovered by scientists at Kyowa Hakko Kirin in Japan.	[51]
	Ganetespib	Second-generation HSP90 inhibitor composed of the resorcinol moiety of radicicol derivatives.	[51]
Miscellaneous	XL888 HSP990 DS2248 TAS-116	Miscellaneous inhibitors, except for TAS-116, all work by binding to the NTD of HSP90.	[52,53]