VU6028418 (VU 6028418) is a potent, highly selective, orally bioavailable M4 mAChR antagonist for the treatment of dystonia and other movement disorders.

VU6019650 is a potent, highly selective M5 mAChR orthosteric antagonist with IC50 of 36 nM, >100-fold selectivity against human M1-4.VU6019650 blocked the nonselective muscarinic agonist oxotremorine-M-induced increases in neuronal firing rates of midbrain dopamine neurons in the ventral tegmental area.VU6019650 also inhibited oxycodone self-administration in male Sprague-Dawley rats without impair general motor output.

VU6015241 (VU 6015241) is a highly potent and selective antagonist of M4 muscarinic acetylcholine receptor (mAChR4) with IC50 of 71 nM.VU6015241 demonstrates selectivity across multiple species, excellent aqueous solubility, and moderate brain exposure in rodents after intraperitoneal administration.

VU6009048 is a potent, selective M4 positive allosteric modulator (PAM) with EC50 of 85 nM (hM4) and 379 nM (rM4).

VU6007215 is a potent, selective M4 positive allosteric modulator (PAM) with EC50 of 144 nM (hM4) and 295 nM (rM4).

VU0468554 (VU 0468554) is a nove potent, selective inhibitor of GIRK channel with IC50 of 0.85 and 2.6 uM for GIRK1/GIRK4 and GIRK1/GIRK2 in cellular assays.VU0468554 more effectively inhibits the cardiac GIRK channel than the neuronal GIRK channel, inhibits Gβγ-activated GIRK channels in noncompetitive and potentially uncompetitive fashion.VU0468554 competitively inhibits GIRK-channel activation by ML297, a GIRK-channel activator.In the isolated heart model, VU0468554 partially reversed carbachol-induced bradycardia in hearts from wild-type mice but not Girk4-/- mice.

VT02956 is a potent, specific inhibitor of Hippo pathway kinase LATS with IC50 of 0.76 nM (LATS1) and 0.52 nM (LATS2), respectively; VT02956 reduces YAP/TAZ phosphorylation in both dose- and time-dependent manner with IC50 of 0.16 μM and 0.43 μM in HEK293A cells and 4T1 cells, respectively. VT02956 suppresses ESR1 transcription, dramaticly reduces ERα and its target genes TFF1 and GREB1. VT02956 targets the LATS-YAP/TAZ-ERα axis to inhibit ER+ tumours cell growth, inhibits the proliferation of MCF-7 and T47D cells. VT02956 inhibits the growth of T47D cells with hormone therapy resistant ESR1 mutation (ERa Y537S or D538G), enhances the anti-tumour effect of palbociclib in ER+ breast cancer cells.

VT02484 is the negative control compound of VT02956, which is a highly potent Hippo pathway kinase LATS inhibitor.

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.

Vornorexant (TS-142, ORN0829) is a potent dual orexin 1 and 2 receptor antagonist with IC50 of 1.05 and 1.27 nM for hOX1R and hOX2R, resepctively.Vornorexant (TS-142, ORN0829) exhibited potent sleep-promoting effects at a po dose of 1 mg/kg in a rat polysomnogram study.Vornorexant (TS-142, ORN0829) is a viable candidate and is currently in clinical development for the treatment of insomnia.

VISTA inhibitor M351-056 is a small molecule compound having affinity with VISTA.

Vercirnon (GSK1605786A, CCX282-B) is a potent, selective, orally bioavailable antagonist of CCR9, inhibits CCR9-mediated Ca2+ mobilization and chemotaxis on Molt-4 cells with IC50 of 5.4 and 3.4 nM, respectively.Vercirnon (GSK1605786A, CCX282-B) displays high selectivity for CCR9 over CCR1-12 and CX3CR1-7 (IC50>10 uM).Vercirnon (GSK1605786A, CCX282-B) is an equipotent inhibitor of CCL25-directed chemotaxis of both splice forms of CCR9 (CCR9A and CCR9B) with IC50 values of 2.8 and 2.6 nM, respectively.CCX282-B also inhibited mouse and rat CCR9-mediated chemotaxis.Inhibition of CCR9 with CCX282-B results in normalization of Crohn's disease such as histopathology associated with the TNF(ΔARE) mice.

V-0219 is a small molecule positive allosteric modulator (PAM) of GLP-1R with Emax of 60% in the cAMP assay.V-0219 potentiated insulin secretion in INS-1 β-cells with EC50 of 0.25 nM, the best response was observed at 0.1 nM, when a fixed concentration of 0.2 nM of GLP-1 was added to the dose-response curve of 9, the maximal response observed reached a plateau at 0.1 nM, with an EC50 value of 0.008 nM.V-0219 shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents.

Utatrectinib (AZD7451, AZ12607092) is a potent, selective, small molecule pan-Trk (NTRK) inhibitor with IC50 of 0.2-3.0 nM against TrkA, TrkB, and TrkC.Binding of AZD7451 to TrkA, TrkB, and TrkC would be expected to inhibit responses associated with NGF, BDNF, and NT3, respectively.AZD7451 completely blocked TrkC activation and associated tumorigenic behaviors at sub-micromolar concentrations in normal salivary gland tissue.AZD7451 showed efficacy and low toxicity in pre-clinical studies on adenoid cystic carcinoma (ACC) tumors engrafted in mice.AZD7451 potently inhibited in vitro growth and proliferation of the KM12 cell line harboring the NTRK1-fusion at 2 nM, AZD7451 inhibited proliferation of H460 cells at 5 nM, with TRKA phosphorylation inhibition.

USP7-866 is a novel potent selective inhibitor of USP7 with IC50 of 0.18 nM; USP7-866 inhibited the growth of p53-mutant small cell lung cancer cell line H526 at a CC50 of 42 nM.

USP5-Cav3.2 inhibitor II-1 is a small molecule inhibitor of USP5-Cav3.2 interaction, without affecting the enzymatic activity of USP5.II-1 inhibited both phases of formalin-induced nocifensive behaviors in mice.Cav3.2 is required for the action of II-1.II-1 also mediated a robust inhibition of mechanical allodynia induced by injury to the sciatic nerve.

USP5 inhibitor 64 is a selective chemical probe (inhibitor) against USP5 deubiquitinase, binds to the USP5 ZnF-UBD (zinc-finger ubiquitin binding domain) with KD of 2.8 uM.USP5 inhibitor 64 is selective over nine proteins containing structurally similar ZnF-UBD domains.USP5 inhibitor 64 inhibits the USP5 catalytic cleavage of a di-ubiquitin substrate in an in vitro assay.

USP30Inh-1 is a potent, selective small molecule USP30 inhibitor with IC50 of 15-30 nM (inhibition of USP30-mediated cleavage of Ub-Rho110).USP30Inh-1 is anticipated to form a covalent linkage with the catalytic cysteine within the USP30 active site.USP30Inh-1 demonstrated good selectivity against >40 known DUB enzymes at 1 uM. USP30Inh-1 (1-10 uM) enhances mitoKeima signal in SHSY5Y cell, increases p-Ser65-Ub in dopaminergic neurones and astrocytes, as well as in Parkin heterozygote fibroblasts.

USP30 inhibitor Q14 peptide is a peptide derived from the transmembrane (TM) domain of USP30 that can target mitochondrial-anchored USP30 directly and increase mitophagy.

USP inhibitor 2 is a broad DUB inhibitor with IC50 of 0.04 and 0.21 uM for USP4 and USP11, also inhibits USP10/16/15/19 with submicromolar potency, forms a covalent adduct with USP11. USP inhibitor 2 does not inhibit USP5 (IC50>100 uM).

USP inhibitor 1 is an irreversible USP inhibitor with submicromolar IC50 of USP4 and its phylogenetic relative USP11, also functionally inhibits USP33, leading to CP110 instability and synergy with ATR inhibition in U2OS cells.

URML-3881 (URML3881) is a potent, specific MEK1/2 inhibitor IC50 of 30 nM in a cell-free kinase inhibition assay.URML-3881 shows no inhibition among a panel of other kinases including MEK 3 and MEK5, which are activated in alternative MAPK signaling pathways.URML-3881 reduces MAPK pathway activity in clear cell ovarian cancer (CCOC).URML-3881 causes reduced CCOC viability due to induction of tumor cell apoptosis and inhibition of proliferation.URML-3881 abrogates cisplatin-induced prosurvival MAPK signaling in CCOC, resulting in durable and dramatic tumor regression in vivo.

UNC5293 (UNC-5293) is a potent, highly selective, orally available inhibitor of MER receptor tyrosine kinase (MERTK) with IC50 0.9 nM, Ki 0.19 nM.UNC5293 exhibits an excellent Ambit selectivity score (S50 (100 nM) = 0.041), and displays 50-100 fold selectivity over other two TAM Receptor member kinases (Tyro3 and Axl).UNC5293 demonstrated potent and selective inhibition of MERTK in cell-based assays. has excellent mouse PK properties (7.8 h half-life and 58% oral bioavailability) and was active in bone marrow leukemia cells in a murine model.

UM-002 is a highly potent, selective, brain penetrant BRD4 bromodomain inhibitor with IC50 of 8.8 and 2.4 nM for BRD4-1 and BRD4-2, respectively.UM-002 is more potent than JQ1 at inhibiting BRD2-1, BRD4-1, and BRD4-2.UM-002 reduces GBM cell proliferation more than JQ1, or the brain penetrant BET inhibitor MK-8628.UM-002 not affect the enzymatic activity of histone deacetylases, histone acetyltransferases.UM-002 inhibits GBM cell proliferation in vitro with EC50 of 0.13 and 0.24 uM for GBM22 cells and GBM39 cells, repectively.UM-002 reduces proliferation of GBM cells co-cultured with cerebral brain organoids, reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors.

Ulotaront (SEP-363856, SEP-856) is a novel psychotropic agent with agonism at trace amine receptor 1 (TAAR1) and 5-HT1A receptors but no appreciable action at dopamine D2 receptors.Ulotaront significantly reduced the ketamine-induced increase in dopamine synthesis capacity.

UCHL1 inhibitor 27 is a potent, selective, covalent UCHL1 inhibitor with IC50 of 90 nM.UCHL1 inhibitor 27 demonstrated exquisite selectivity in a cross-screening against 20 DUBs.UCHL1 inhibitor 27 demonstrated >50% fibroblast–myofibroblast transition (FMT) inhibition (IC50=100 nM) in idiopathic pulmonary fibrosis (IPF), as well as αSMA inhibition.UCHL1 inhibitor 27 is a powerful and selective probe to explore UCHL1 activity with potential application to substrate identification, mode of action studies, and cellular target profiling.

UBD253 (SGC-UBD253) is a potent, selective ubiquitin chemical probe for ubiquitin binding domain of HDAC6 with Kd of 84 nM (SPR), inhibits the HDAC6-ISG15 interaction (EC50=1.9 uM, nanoBRET).UBD253 (SGC-UBD253) displays little to no affinity for other USPs (>100-fold selectivity). SGC-UBD253 potently (<100 nM) binds HDAC6-UBD (ubiquitin binding domain), decreases the interaction between full-length HDAC6 with ISG15.

UbcH5c inhibitor DHPO is a small molecule UbcH5c inhibitor, directly targets UbcH5c with KD of 37.5 uM.DHPO effectively engaged by the UbcH5c protein in both Panc1 and SW1990 cells.DHPO exerts significant growth inhibition in pancreatic cancer cells in vitro (IC50=2.3-8.5 uM), prevents the migration and invasion of both Panc1 and SW1990 cells.DHPO inhibits pancreatic cancer cell growth and metastasis by inhibiting the NF-κB pathway.DHPO suppresses orthotopic pancreatic tumor growth in vivo, without causing significant host toxicity.DHPO prevents metastasis of pancreatic cancer in vivo.

UAMC-2526 (UAMC2526) is a low micromolar ATG4B and autophagy inhibitor.UAMC-2526 (50-100 uM) completely inhibits proliferation of HT-29 colorectal carcinoma cells.UMAC-2526 inhibits autophagy in a colorectal cancer xenograft model and potentiates chemotherapy efficacy.UMAC-256 inhibits autophagy in a healthy mouse model, animals treated withcompound UAMC-2526 showed lower levels of uncleaved (free) GFP, decreased LC3-II/LC3-I ratios and a marked increase of SQSTM1.UAMC-2526 combined with gemcitabine significantly reduced tumor growth as compared to the individual treatments, did not inhibit autophagy in the Panc02 mouse model.

UAMC-03011 is a potent anti-trypanosomal compound (IC50=0.63 uM, T. brucei).UAMC-03011 displays selectivity for Trypanosoma brucei over a panel including Trypanosoma cruzi, L.eishmania infantum, and Plasmodium falciparum (IC50>64 uM).