HDAC6 Inhibitor

Nanatinostat (CHR-3996) is a potent, class I selective and orally active HDAC inhibitor with IC₅₀s of 3 nM, 4 nM, and 7 nM for HDAC1, HDAC2, and HDAC3, respectively. Nanatinostat has low activity against HDAC5 (IC₅₀ of 200 nM) and HDAC6 (IC₅₀ of 2100 nM). Nanatinostat induces apoptosis in myeloma cells. Nanatinostat has potent anticancer effects, such as myeloma, advanced solid tumours and colorectal cancer.

KA2507 is a potent, orally active and selective HDAC6 inhibitor, with an IC₅₀ of 2.5 nM. KA2507 shows antitumor activities and immune modulatory effects in preclinical models.

HDAC3-IN-T247 is a potent and selective HDAC3 (histone deacetylase 3) inhibitor, with an IC₅₀ of 0.24 µM. HDAC3-IN-T247 induces a selective increase of NF-κB acetylation in HCT116 cells. HDAC3-IN-T247 shows anticancer and antiviral activity. HDAC3-IN-T247 inhibits growth of cancer cells, and activates HIV gene expression in latent HIV-infected cells.

SE-7552, a 2-(difluoromethyl)-1,3,4-oxadiazole (DFMO) derivative, is an orally active, highly selective, non-hydroxamate HDAC6 inhibitor with an IC₅₀ of 33 nM. SE-7552 is greater than 850-fold selectivity versus all other known HDAC isozymes. SE-7552 is capable of blocking multiple myeloma growth in vivo. SE-7552 acts as an anti-obesity agent in diet-induced obese mice.

LSD1/HDAC6-IN-2 (JBI-802) is an orally active LSD1/HDAC6/MAO-A inhibitor, with IC₅₀ values of 5 nM, 11 nM, and 5 nM, respectively. LSD1/HDAC6-IN-2 can inhibit the growth of multiple myeloma cells MM.1S, MM.1R, and RPMI-8226. LSD1/HDAC6-IN-2 can be used for research on diseases such as acute myeloid leukemia and lymphoma.

HDACs/mTOR Inhibitor 1 is a dual HDACs and mTOR inhibitor, with IC₅₀s of 0.19 nM, 1.8 nM, 1.2 nM for HDAC1, HDAC6, mTOR, respectively. HDACs/mTOR Inhibitor 1 stimulates cell cycle arrest in G0/G1 phase and induces tumor cell apoptosis with low toxicity in vivo. HDACs/mTOR Inhibitor 1 can be used in the research of hematologic malignancies.

J22352 is a PROTAC (proteolysis-targeting chimeras)-like and highly selective HDAC6 inhibitor with an IC₅₀ value of 4.7 nM. J22352 promotes HDAC6 degradation and induces anticancer effects by inhibiting autophagy and eliciting the antitumor immune response in glioblastoma cancers, and leading to the restoration of host antitumor activity by reducing the immunosuppressive activity of PD-L1.

MPT0G211 is a potent, orally active and selective HDAC6 inhibitor (IC₅₀=0.291 nM). MPT0G211 displays >1000-fold selective for HDAC6 over other HDAC isoforms. MPT0G211 can penetrate the blood-brain barrier. MPT0G211 ameliorates tau phosphorylation and cognitive deficits in an Alzheimer’s disease model. MPT0G211 has anti-metastatic and neuroprotective effects. Anticancer activities.

Givinostat (ITF-2357) hydrochloride is a HDAC inhibitor with an IC₅₀ of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat hydrochloride can penetrate the blood-brain barrier (BBB)..

BG45 is a potent HDAC3 inhibitor with IC₅₀ values of 0.289, 2, 2.2 and ﹥20 μM for HDAC3, HDAC1, HDAC2 and HDAC6, respectively. BG45 selectively targets multiple myeloma (MM) cells and induces caspase-dependent apoptosis.

Resminostat hydrochloride is a potent inhibitor of HDAC1, HDAC3 and HDAC6, with mean IC₅₀ values of 42.5, 50.1, 71.8 nM, respectively, and shows less potent activities against HDAC8, with an IC₅₀ of 877 nM.

PROTAC HDAC6 degrader 2 is a non‑hydroxamate selective HDAC6 PROTAC degrader with an IC₅₀ of 0.643 μM and shows high selectivity for HDAC6 over HDAC1-4. PROTAC HDAC6 degrader 2 recruits VHL E3 ubiquitin ligase to trigger HDAC6 ubiquitination and subsequent proteasomal degradation. PROTAC HDAC6 degrader 2 selectively elevates acetylated α-tubulin levels in cancer cells, and does not induce histone H3 hyperacetylation or obvious loss of cell viability. PROTAC HDAC6 degrader 2 is applicable for research on multiple myeloma.

Bavarostat (EKZ-001) is a blood-brain barrier-permeable, potent HDAC6 inhibitor and PET radiotracer, with an IC₅₀ as low as 17 nM against human HDAC6. Bavarostat can be labeled with ¹⁸F and used as a probe to map HDAC6 distribution and measure target occupancy in the brains of non-human primates. Bavarostat also selectively modulates tubulin acetylation, but not histone acetylation. Bavarostat is applicable for research on Alzheimer's disease, other neurodegenerative disorders, and cancers.

Imofinostat (ABT-301; MPT0E028) is an orally active and selective HDAC inhibitor with IC₅₀s of 53.0 nM, 106.2 nM, 29.5 nM for HDAC1, HDAC2 and HDAC6, respectively. Imofinostat has a weak inhibitory effect on HDAC8 (IC₅₀ of 2.5 ​​μM), but no inhibitory effect on HDAC4 (IC₅₀>10 μM). Imofinostat reduces the viability of B-cell lymphomas by inducing apoptosis and possesses potent direct Akt targeting ability and reduces Akt phosphorylation in B-cell lymphoma. Imofinostat has a broad-spectrum antitumor activity, including colorectal cancer, B-cell lymphoma, non-small cell lung carcinoma (NSCLC), and pancreatic cancer, while also showing therapeutic potential in non-tumor diseases like emphysema and pulmonary fibrosis.

HPB (HDAC6 inhibitor HPB) is a selective HDAC6 inhibitor with an IC₅₀ of 31 nM. HPB exhibits >30-flod selectivity for HDAC6 over HDAC1.

DNMT/HDAC-IN-1 (Compund 15a) is a dual DNMT and HDAC inhibitor with IC₅₀ values for HDAC1 and HDAC6 are 56.84 nM and 17.39 nM respectively. DNMT/HDAC-IN-1 can induce apoptosis and be used in tumor research.

Crebinostat is a potent histone deacetylase (HDAC) inhibitor with IC₅₀ values of 0.7 nM, 1.0 nM, 2.0 nM and 9.3 nM for HDAC1, HDAC2, HDAC3 and HDAC6, respectively. Crebinostat potently induces acetylation of both histone H3 and histone H4 as well as enhances the expression of the cAMP response element-binding protein (CREB) target gene Egr1. Crebinostat increases the density of synapsin-1 punctae along dendrites in cultured neurons. Crebinostat can modulate chromatin-mediated neuroplasticity and exhibits enhanced memory in mice.

WT-161 is a potent and selective HDAC6 inhibitor with an IC₅₀ of 0.40 nM. WT-161 also inhibits metallo-β-lactamase domain-containing protein 2 (MBLAC2).

CG347B is a selective HDAC6 inhibitor, also involves in synthesis of other metalloenzyme inhibitors. HDAC6 inhibitors can be used for oncology, immunology, and neurology research.

BRD2492 (compound 6d) is a potent, selective HDAC1 and HDAC2 inhibitor with IC₅₀s of 13.2 nM and 77.2 nM, respecrtively. BRD2492 exhibits >100-fold selectivity for HDAC1/2 over selectivity over HDAC3 and HDAC6. BRD2492 inhibits breast cancer cell lines growth with IC₅₀s of 1.01 μM and 11.13 μM for T-47D and MCF-7 cells, respectively.