hsp90α

Debio 0932 (CUDC-305) is a heat shock protein 90 (Hsp90) inhibitor that targets the n-terminal atp-binding pocket to promote apoptosis, and has the advantage of being orally available and able to cross the blood-brain barrier (BBB) for the treatment of cancers such as non-small-cell lung cancer (NSCLC) and neuroblastoma.

Luminespib (VER-52296) is an HSP90 inhibitor that inhibits HSP90α and HSP90β (IC50=7.8 21 nM). Luminespib has antitumor activity and is used in studies of head and neck tumors, among others.

SNX2112 (PF 04928473) is an orally active Hsp90 inhibitor, with a Kd of 16 nM.

NVP-HSP990 (HSP990) is an effective and specific HSP90α β inhibitor (IC50: 0.6 0.8 nM).

Compound X10g (PROTAC Hsp90α degrader 1) is a selective agent targeting Hsp90α for degradation and is utilized in breast cancer research. It demonstrates inhibitory effects on the proliferation of breast cancer cell lines, MDA-MB-231, MDA-MB-468, MCF-7, and MX-1, with respective IC50 values of 51.48 μM, 16.46 μM, 8.93 μM, and 11.95 μM [1].

Tamoxifen (ICI47699) is a selective and orally effective estrogen receptor modulator (SERM). Tamoxifen has both inhibitory (e.g., mammary cells) and activating (e.g., bone, liver, and uterine cells) activity against estrogens.

Tamoxifen is an antineoplastic nonsteroidal selective estrogen receptor modulator (SERM).

Alvespimycin hydrochloride (BMS 826476) is a potent HSP90 inhibitor with IC50 of 62 nM. Phase 2.

Onalespib (AT13387) is a synthetic, orally bioavailable, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Onalespib selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability and degradation of many oncogenic signaling proteins.

Tanespimycin (KOS 953) (17-AAG) is an inhibitor of Hsp90 that selectively inhibits BT474 tumor cell Hsp90 (IC50: 5 nM).

BIIB021 (CNF2024) is an orally-available, fully synthetic inhibitor of HSP90(Ki=1.7 nM, EC50=38 nM).

PF04929113 (SNX-5422) is a synthetic, novel, small molecule Hsp90 Inhibitor. As an oral formulation that demonstrates strong efficacy and tolerability, PF04929113 is positioned as a breakthrough therapy with broad applicability across a wide range of cancers.

CCT018159 is a 3,4-diarylpyrazole resorcinol, an ATP-competitive HSP90ATPase inhibitor that inhibits human Hsp90β and yeast Hsp90 with IC50s of 3.2 and 6.6 μM, respectively.CCT018159 inhibits key endothelial and tumor cell functions associated with invasion and angiogenesis. CCT018159 caused cellular inhibition associated with G1 phase block and induced apoptosis.

Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Gedunin is an Hsp90 inhibitor, and inhibits ovarian cancer cell proliferation.

Eupalinolide B is a natural product ,and demonstrates potent cytotoxicity against A-549, BGC-823, SMMC-7721, and HL-60 tumour cell lines.

Grp94 Inhibitor-1 is a potent and selective inhibitor of Grp94 with an IC50 of 2 nM.

KW-2478 is a non-ansamycin HSP90 inhibitor with IC50 of 3.8 nM.

PU-H54 is a purine-based inhibitor of Grp94. It is a Grp94-selective resorcinol-based inhibitor isolated through probing of the exclusive binding region of S2 subpocket in Grp94.

CH5138303 is an orally available Hsp90 inhibitor with Kd of 0.48 nM.

Derrubone, an isoflavone natural product derived from Derris robusta, is considered an effective Hsp90 inhibitor. It binds strongly to the CTD of Hsp90α and induces the degradation of tau proteins, which may be viewed as a potential treatment approach for Alzheimer's disease (AD).

EC 144, a second-generation selective inhibitor of Hsp90 (heat shock protein 90), inhibits tumor growth with an IC50= 1.1 nM for Hsp90α and an EC50 = 14 nM for degradation of Her-2 in MCF-7 cells.

Pimitespib (TAS-116) is an ATP-competitive and highly specific HSP90α HSP90β inhibitor with inhibition constants (Kis) of 34.7 nM and 21.3 nM, respectively.

HSP90-IN-11 is a potent inhibitor of HSP90 and induces significant accumulation of the sub-G1 population. HSP90-IN-11 has a potent HSP90α inhibitory effect comparable to that of AUY-922 (Luminespib). In CRC and NSCLC cells, HSP90-IN-11 exhibited significant anti-proliferative activity in the double-digit nM range.HSP90-IN-11 was able to rapidly degrade client proteins EGFR and Akt in NSCLC cells.

NDNA4 (compound 17) is a selective Hsp90α inhibitor (IC50: 0.34 μM) with permanent charge and low membrane permeability. It demonstrates minimal cytotoxicity against Ovcar-8 and MCF-10A cell lines (IC50 >100 μM) and maintains hERG channel maturation without triggering a heat shock response or degrading Hsp90α-dependent client proteins [1].