KUSC-5037 (KUSC5037) is a novel effective HIF-1 inhibitor with IC50 of 1.2 uM against HIF-1 transcriptional activity.KUSC-5037 suppressed the HIF-1α (a regulatory subunit of HIF-1) mRNA, causing decreases in the gene expression of HIF-1 target genes such as carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) genes.KUSC-5037 directly targets ATP5B protein, a catalytic β subunit of mitochondrial FoF1-ATP synthase.

KYN-101 (KYN101) is a potent, selective synthetic antagonist of aryl hydrocarbon receptor (AHR) with IC50 of 22 nM in human HepG2 DRE-luciferase reporter assay and 23 nM in murine Hepa1 Cyp-luc assay.KYN-101 reverses IDO/TDO-mediated tumor progression and improves the efficacy of PD-1 blockade in B16 IDO tumor-bearing mice, as well as CT26 colorectal cancer model expressing endogenous high levels of IDO.

LEO 134310 (LP 0155) is a non-steroidal, potent and selective glucocorticoid receptor (GR) agonist (EC50=2 nM, hPBMC)

MB 07811 (MB07811) is an orally bioavailable, liver-targeted prodrug of MB07344, which is a thyroid hormone receptor-beta agonist (TRβ) agonist, efficiently converted to MB07344 by liver microsomes in vivo; reduces cholesterol and both serum and hepatic triglycerides at doses devoid of effects on body weight, glycemia, and the THA.

MSU 38225 (MSU-38225) is a novel small molecule that inhibit the Nrf2 pathway, potentially inhibiting Nrf2 transcriptional activity and cancer cell growth; MSU38225 downregulates Nrf2 transcriptional activity and decreases the expression of Nrf2 downstream targets, including NQO1, GCLC, GCLM, AKR1C2, and UGT1A6. MSU38225 strikingly decreases the protein level of Nrf2, which can be blocked by the proteasome inhibitor MG132. Ubiquitination of Nrf2 is enhanced following treatment with MSU38225. By inhibiting production of antioxidants, MSU38225 increases the level of reactive oxygen species (ROS) when cells are stimulated with tert-butyl hydroperoxide (tBHP). MSU38225 also inhibits the growth of human lung cancer cells in both two-dimensional cell culture and soft agar.

MYCMI-7 is a small molecule MYC-binding compound (Kd=4 uM) that inhibits MYC-MAX interaction.MYCMI-7 efficiently and selectively inhibits MYC:MAX and MYCN:MAX interactions in cells, binds directly to recombinant MYC, and reduces MYC-driven transcription.MYCMI-7 induces degradation of MYC and MYCN proteins.MYCMI-7 potently induces growth arrest/apoptosis in tumor cells in a MYC/MYCN-dependent manner and downregulates the MYC pathway on a global level.MYCMI-7 downregulates MYC/MYCN, inhibits tumor growth, and prolongs survival through apoptosis in mouse tumor models of MYC-driven AML, breast cancer, and MYCN-amplified neuroblastoma.

NXT629 (NXT-629) is a potent, selective PPARα antagonist with IC50 of 77 nM (human PPARα), no effect against PPARδ and PPARγ (IC50>30 uM).NXT629 inhibited agonist-induced transcription of PPARα-regulated genes, demonstrating target engagement in chronic lymphocytic leukemia (CLL) cells.NXT629 induced apoptosis of CLL cells even in the presence of a protective microenvironment.NXT629 reduces the number of chronic leukemia cells undergoing cell division with IC50 of 9.6 uM.NXT629 reduces CLL tumor burden delays disease progression of CLL in CLL mouse model.

PKUMDL-YC-1205 is a specific small molecule that can specifically bind to the disordered bHLH-LZ domain of c-Myc (SPR kd=18 uM).PKUMDL-YC-1205 abrogates cell proliferation of HL-60 cells with IC50 of 40 uM, blocks the interaction between c-Myc370–409 and Max.

PPARγ pSer273-IN-10 is a specific, in vivo-active small molecule inhibitor of CDK5-mediated Ser273 phosphorylation of PPARγ without classical PPARγ agonism.PPARγ pSer273-IN-10 is a potent PPARγ binder and in vitro inhibitor of the CDK5-mediated phosphorylation of PPARγ Ser273 and displays negligible PPARγ agonism in a reporter gene assay. PPARγ pSer273-IN-10 demonstrated an improvement in insulin sensitivity in the ob/ob diabetic mouse model in 7 day treatment in vivo testing.

PRL295 is a small molecule Keap1-Nrf2 protein–protein interaction inhibitor.PRL295 binds to Keap1 in the cellular environment, disrupting its interaction with Nrf2, which leads to enhanced gene expression of the classical Nrf2 target NQO1 in cells and in vivo in the mouse liver.PRL-295 increases the thermostability of Keap1 in cell lysates and in live cells.PRL 295 decreased the levels of plasma alanine aminotransferase and aspartate aminotransferase upon acetaminophen-induced hepatic injury.

Rohinitib is a potent and specific inhibitor of eIF4A1, inhibits growth and survival of AML cells especially cells with FLT3-ITD.

SR1555 is a selective RORγ inverse agonist (IC50=1.5 uM) that suppresses T(H)17 cells and stimulates T regulatory cells; SR1555 is devoid of LXR, FXR, and RORα activity, displaces [3H]T0901317 from the ligand binding domain (LBD) of RORγ with IC50 of 1 uM; represses the expression of RORγ while leading to increased expression of FGF21 and adipoQ in pre-adipocyctes, inhibits activation of hormone-sensitive lipase and increased fatty acid oxidation in obese diabetic mice.

TTC352 is a synthetic selective estrogen mimic acts as estrogen receptor (ER) partial agonist for the treatment of endocrine-resistant breast cancer.TTC 352 yields an H-bond with Glu353, allows Asp351-to-helix 12 (H12) interaction, sealing ERα's ligand-binding domain, recruiting E2-enriched coactivators, and triggering rapid ERα-induced unfolded protein response (UPR) and apoptosis.TTC-352 is a less potent full estrogen agonist compared to E2, allowing H12 to seal the LBD, which recruits many E2-enriched coactivators, and induces rapid ERα-mediated UPR and apoptosis.

VPC-13789 (VPC13789) is a potent, selective, orally available inhibitor of androgen receptor binding function-3 (BF3) site.VPC-13789 suppresses AR-mediated transcription, chromatin binding, and recruitment of coregulatory proteins.VPC-13789 selectively reduces the growth of both androgen-dependent and enzalutamide-resistant PCa cell lines.VPC-13789 demonstrated in vitro efficacy that reduced PSA production and tumor volume in animal models of CRPC with no observed toxicity.

VT104 (VT-104) is a specific small molecule inhibitor of YAP/TAZ-TEAD-dependent transcription with IC50 of 10.4 nM in YAP reporter assay, pan-TEAD palmitoylation inhibitor.VT104 inhibited palmitoylation of both endogenous TEAD1, TEAD3 proteins in cells.VT104 decreased the levels of palmitoylated TEAD3 and TEAD4 and increased the levels of unpalmitoylated TEAD3 and TEAD4 in the human mesothelioma cell line NCI-H2373.VT104 exhibited inhibitory activity in more mesothelioma cell lines than the TEAD1-selective inhibitor VT103.VT104 (oral administration of 10 and 3 mg/kg) has very strong antitumor efficacy in the human mesothelioma NCI-H226 CDX model, with no effect on body weight gain.

WBC100 (WBC-100) is a novel potent, oral active that selectively degrades c-Myc protein over other proteins and potently kills c-Myc overexpressing cancer cell.selectively kills c-Myc overexpressing cancer cells Mia-paca2 (PDAC), H9 (T-cell lymphoma), andMOLM-13 (acute myeloid leukemia) with IC5 of 61, 17 and 16 nM, respectively.WBC100 targets the nuclear localization signal 1 (NLS1)-Basic-nuclear localization signal 2 (NLS2) region of c-Myc and induces c-Myc protein degradation through ubiquitin E3 ligase CHIP mediated 26S proteasome pathway, leading to apoptosis of cancer cells.WBC100 potently regresses multiple lethal c-Myc overexpressing tumors such as acute myeloid leukemia, pancreatic, and gastric cancers with good tolerability in multiple xenograft mouse models.

WO95E is a novel potent, synthetic ligand (partial agonist) of PPARγ, directly binds to PPARγ with IC50 of 11 nM; WO95E's binding affinity is approximately 70-fold lower than that of UHC1 (Journal of Biological Chemistry. 2014;289(38):26618–26629.). WO95E significantly inhibited the S273 phosphorylation of PPARγ in 3T3-L1 differentiated adipocytes, led to the upregulation of the mRNA levels of a number of the PPARγ phosphorylation-dependent genes, including adiponectin, cycp2f2, Ddx-17, Rarres2, and Selenbp1. Unlike SR1664 and UHC1, WO95E does not bind to the canonical PPARγ ligand-binding pocket (LBP) containing H3, H3-4 loop, H11 and H12, which full agonist Rosi binds, instead, WO95E binds to the ABP comprising H2′-H3, β-sheet, and the Ω loop. WO95E improved glucose tolerance and insulin sensitivity in DIO mice.

YQ-0629 is a specific HIF-2α inhibitor, binds to HIF-2α PAS-B domain with Kd of 57.5 uM.YQ-0629 could inhibit the expression of HIF-2α with or without the presence of PTX (3 nM) in MCF7 MS culture, does not bind to HIF-1α or affect the expression of HIF-1α.YQ-0629 suppresses self-renewal capacity and synergizes with PTX to reverse the chemoresistance of MCF7 MS.YQ-0629 inhibits growth of BCSCs derived from breast cancer patients and synergistically increases anti-BCSCs activity of PTX in vivo.

BNS is a cell penetrant, potent and selective PHD2 (prolyl-hydroxylase 2) inhibitor.

DDO-7263, a 1,2,4-Oxadiazole derivative, is a potent Nrf2 activator. DDO-7263 upregulates Nrf2 through binding to Rpn6 to block the assembly of 26S proteasome and the subsequent degradation of ubiquitinated Nrf2. DDO-7263 activates the Nrf2-ARE signaling pathway and exerts anti-inflammatory activity.

Hydrocortisone aceponate (Hydrocortisone 17-propionate 21-acetate) is a potent topical glucocorticoid. Hydrocortisone aceponate can be used for various dermatoses research.

S26948 is a specific peroxisome proliferator-activated receptor γ (PPARγ) modulator (EC50=8.83 nM) with potent antidiabetes and antiatherogenic effects. S26948 is a specific high-affinity agonist for PPARγ.