heterodimerization

Amitriptyline hydrochloride (Annoyltin) is the hydrochloride salt of the tricyclic dibenzocycloheptadiene amitriptyline with antidepressant and antinociceptive activities.

1. Dehydrocorydaline (13-Methylpalmatine) exerts anti-metastatic potential via suppression of MMPs and Bcl-2 signaling in NSC-LC cells. 2. Dehydrocorydaline stimulates p38 MAPK activation, which can enhance heterodimerization of MyoD and E proteins, thus resulting in MyoD activation and myoblast differentiation. 3. Dehydrocorydaline shows antiplatelet effects, it inhibits thrombin-induced platelet aggregation in a low dose ( IC50= 34.914 ug mL). 4. Dehydrocorydaline has anti-inflammatory and antinociceptive effects. 5. Dehydrocorydaline inhibits MCF-7 cell proliferation by inducing apoptosis mediated by regulating Bax Bcl-2, activating caspases as well as cleaving PARP.

GN44028 (N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1,4-dihydroindeno[1,2-c]pyrazol-3-amine) is a hypoxia-inducible factor inhibitor of (HIF)-1 (IC50: 14 nM). GN44028 inhibits hypoxia-induced HIF-1α transcriptional activity. However, It can not be suppressing HIF-1α mRNA expression, HIF-1α protein accumulation, or HIF-1α HIF-1β heterodimerization.

Cucurbit[8]uril is a highly effective and safe supramolecular compound that promotes protein heterodimerization. It selectively induces the heterodimerization of methylviologen and naphthalene functionalized proteins, demonstrating its specificity and versatility. Additionally, Cucurbit[8]uril shows exceptional oral activity and low toxicity, making it a promising candidate for various pharmaceutical and biotechnological applications.

RdRP-IN-8 (compound 45) is an antiviral agent targeting influenza viruses. It inhibits the viral RNA-dependent RNA polymerase (RdRP) activity by disrupting the heterodimerization of the PA and PB1 subunits, with an IC50 value of 0.13 μM.

TAT-cyclo-CLLFVY TFA is a cyclic peptide inhibitor targeting HIF-1 heterodimerization to mitigate hypoxia signaling within cancer cells. It effectively disrupts the protein-protein interaction between HIF-1α and HIF-1β, with an inhibitory concentration (IC 50) of 1.3 μM [1].

NPAS3-IN-1 is a potent inhibitor of NPAS3-ARNT heterodimerization, modulating NPAS3 transcription by targeting the interaction between NPAS3 and ARNT at the cellular level.

PT2399 shows effective antitumor activity in vivo. PT2399 is an effective and selective HIF-2α antagonist, which directly binds to the HIF-2α PAS B domain (IC50: 6 nM).

APS-2-79 hydrochloride (APS-2-79 HCl) is a MAPK antagonist that modulating KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK.

Anticancer agent 135 (compound 26h) is a potent androgen receptor (AR) antagonist that blocks AR nuclear translocation and inhibits AR AR-V7 heterodimerization to suppress downstream gene transcription, demonstrating strong efficacy in prostate cancer xenograft models [1].

T1001 is an antagonist of hypoxia-inducible factor-2α subunit (HIF-2α) which displaces residue M252 from inside the HIF-2α PAS-B pocket toward the ARNT subunit to weaken heterodimerization.

CP61, a cyclic peptide, functions as a dual inhibitor of CtBP1 CtBP2. It binds to CtBP1 with an affinity of 3 μM and inhibits both heterodimerization and homodimerization of CtBP2 with an IC50 value of 19 μM. CP61 shows promise for cancer research.

TC-S 7009 is a potent and selective HIF-2α inhibitor (Kd: 81 nM) with significantly higher affinity for HIF-2α than HIF-1α (Kd >> 5μM). TC-S 7009 disrupts HIF-2α heterodimerization, reduces HIF-2α target gene expression, and diminishes DNA binding activity.

Brimarafenib is a selective RAF dimerization inhibitor, which can inhibit the activity of BRAF and CRAF, and exhibits significant inhibitory effects on a variety of RAF mutations (including BRAF I II III mutations, BRAF fusion and CRAF heterodimerization), and is used for the treatment of colorectal and pancreatic cancers and other solid tumors with MAPK mutations.