| DC70579 |
M3258
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M3258 (M 3258) is a potent, reversible, highly selective and orally acitve LMP7 inhibitor with ceullar IC50 of 4.1 nM.M3258 does not inhibit other constitutive proteasome and immunoproteasome subunits (IC50>2.5 uM).M3258 demonstrated strong antitumor efficacy in multiple myeloma xenograft models.M3258 treatment led to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells both in vitro and in vivo.M3258 showed superior antitumor efficacy in selected multiple myeloma and mantle cell lymphoma xenograft models compared with the approved nonselective proteasome inhibitors bortezomib and ixazomib. |
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| DC70580 |
M3541
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M3541 (M 3541) is a novel potent, selective and ATP-competitive ATM kinase inhibitor with IC50 of 0.25 nM (ATP, 10 uM).M3541 displays a good margin of selectivity (>60-fold) against the closely related PIKK family members with DNA-PK, PI3K isoforms, mTOR, and ATR.M3541 inhibits the phosphorylation of ATM as well as its cellular substrates CHK2, KAP1, and p53 in a concentration-dependent manner in A549 cells.M3541 inhibits double strand break repair and sensitizes cancer cells to radiation.M3541 suppresses ATM pathway activity and potentiates radiation efficacy in xenograft models of human cancer, synergizes with topoisomerase and PARP inhibitors. |
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| DC70589 |
MC-GGFG-DX8951
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MC-GGFG-DX8951 is a drug-linker conjugate for ADC with antitumor activity by using DX8951 (DNA topoisomerase I inhibitor), linked via the protease cleavable MC-GGFG linker. |
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| DC70590 |
MCI-INI-3
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MCI-INI-3 is a potent, selective, competitive inhibitor of ALDH1A3 (Ki=0.55 uM), shows poor inhibitory effect on the structurally related isoform ALDH1A1 (>140-fold selectivity).MCI-INI-3 also displays on inhibition against six isoforms of ALDH (ALDH16A1, ALDH7A1, ALDH9A1, ALDH2, ALDH1B1, ALDH18A1).MCI-INI-3 demonstrates selective binding to ALDH1A3 in glioma stem cell lysates, inhibits ALDH activity and affects RA synthesis in cells. |
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| DC70591 |
mCLB073
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mCLB073 is an advanced, orally active small molecule agonist specifically designed to target Mtb adenylyl cyclase Rv1625c. As an optimized derivative of V-59, it demonstrates significantly enhanced potency and efficacy for in vivo applications. In cholesterol-based media, mCLB073 shows a remarkable 17-fold increase in activity against Mtb compared to its predecessor, V-59, while retaining favorable pharmacokinetic characteristics and a strong safety profile. In preclinical studies, oral administration of mCLB073 at 30 mg/kg led to a substantial reduction in Mtb colony-forming units (CFUs) in the lungs of mice, accompanied by a 45% decrease in lung pathology severity. These findings highlight its potential as a promising therapeutic candidate for tuberculosis treatment. |
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| DC70592 |
MCUF-651
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MCUF-651 (MCUF651) is a small molecule guanylyl cyclase A receptor (GC-A) positive allosteric modulator (PAM), potentiate ANP-mediated cGMP with EC50 of 0.45 uM (Emax=82%) in HEK293 GC-A cells.MCUF-651 enhanced ANP-mediated cGMP generation in human cardiac, renal, and fat cells and inhibited cardiomyocyte hypertrophy in vitro.MCUF-651 binds to GC-A (Kd=397 nM) and selectively enhances the binding of ANP to GC-A ( MCUF-651+ANP, Kd=0.06 nM).MCUF-651 is orally bioavailable in mice and enhances the ability of endogenous ANP and BNP to generate GC-A-mediated cGMP ex vivo. |
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| DC70595 |
MFH290
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MFH290 (MFH-290) is a potent, highly selective, covalent inhibitor of CDK12/13 with IC50 of 25/49 nM.MFH290 forms a covalent bond with Cys-1039 of CDK12, and CDK12-dependent as mutation of Cys-1039 rendered the kinase refractory to MFH290.MFH290 exhibits excellent kinome selectivity, inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II), and reduces the expression of key DNA damage repair genes.MFH290 restored Pol II CTD phosphorylation and DNA damage repair gene expression AND augments the antiproliferative effect of the PARP inhibitor olaparib. |
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| DC70599 |
miR-21 inhibitor 12
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miR-21 inhibitor 12 (miR-21-IN-12) is a small molecule inhibitor of microRNA-21 expression and inhibit miR-21 transcription.miR-21-IN-12 inhibited transcription of the miR-21 gene resulting in significant reductions in primary and mature miR-21 levels.miR-21-IN-12 demonstrated cytotoxicity in a cervical cancer cell line via induction of apoptosis and was capable of reducing microtumor formation in a long-term clonogenic assay.miR-21-IN-12 shows some level of selectivity for miR-21 and is not a general miRNA pathway inhibitor. |
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| DC70602 |
ML339
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ML 339 is a potent and selective hCXCR6 antagonist (IC50 = 140 nM), 100-fold less active at the murine CXCR6 receptor (IC50 = 18 uM);
ML 339 exhibits selectivity over CXCR5, CXCR4, CCR6 and APJ receptors. |
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| DC70605 |
ML307
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ML307 is a potent, sub-micromolar (IC50=781 nM), first-in-class, small molecule inhibitor of Ubc13 enzyme activity, >128-fold selective against Caspase-3 and Bfl-1. |
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| DC70609 |
MMV030084
Featured
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MMV030084 (MMV-030084) is a potent, specific P. falciparum cGMP-dependent protein kinase (PKG) inhibitor (Kdapp=9-16 nM), inhibits invasion of P. berghei ANKA parasites into HepG2 liver cells with IC50 of 199 nM.MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation, shows potent activity against liver, asexual, and sexual blood stage development.MMV030084 showed an IC50 of 109 nM against the drug-sensitive 3D7-A10 line, and an IC50 of 120 nM against multidrug-resistant Dd2-B2 parasites in a 72-h growth inhibition assay against Pf ABS parasites.MMV030084 inhibited male gamete exflagellation at an IC50 of 141 nM when gametocytes were stimulated to develop into male gametes.MMV030084 is a promising Plasmodium PKG-targeting chemotype. |
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| DC70618 |
MS177
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MS 177 (MS-177) is a potent and selective EZH2 degarder (PROTAC) based on EZH2 inhibitor C24 with CRBN ligand pomalidomide with DC50 of 0.2 uM in EOL-1 cells.MS177 effectively degraded cellular EZH2-PRC2, suppressed global H3K27me3 in leukaemia cells.MS177 exhibited half-maximal degradation concentration (DC50) values of 0.2 ± 0.1 μM and 1.5 ± 0.2 μM, and maximum degradation (Dmax) values of 82% and 68%, respectively, in EOL-1 and MV4;11 cells.MS177 efficiently suppresses EZH2-PRC2 functions, also efficiently induces Myc degradation in cancer cells, suppresses EZH2-PRC2 functions.MS177 efficiently induces leukaemia cell growth inhibition, apoptosis and cell cycle progression arrest, which is more effective than EZH2 inhibitors. MS177 (i.p. injection, 50-1 g/kg) represses AML growth without apparent toxicity in PDX models. |
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| DC70620 |
MS934
Featured
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MS934 (MS-934) is a VHL-recruiting MEK1/2 degrader (PROTAC) with HT29 DC50 of 18/9 nM for MEK1/2 degradation, respectively.MS934 is more potent at inhibiting the growth of HT-29, SK-MEL-28, H3122, and SUDHL1 cells. MS934 also displays good plasma exposure in mice. |
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| DC70621 |
MS9715
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MS9715 (MS-9715) is a NSD3-targeting PROTAC designed by linking BI-9321, a NSD3 antagonist, which binds NSD3's PWWP1 domain, with an E3 ligase VHL ligand.MS9715 achieves effective and specific targeting of NSD3 and associated cMyc node in tumor cells.MS9715 effectively suppresses growth of NSD3-dependent hematological cancer cells.MS 9715 effectively suppresses NSD3-and cMyc-associated gene expression programs, resembling effects of the CRISPR-Cas9-mediated knockout of NSD3. |
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| DC70623 |
MSU38225
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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. |
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| DC70631 |
MYCMI-7
Featured
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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. |
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| DC70634 |
N8279
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N8279 (NCATS-SM8864) is a selective, brain-penetrant small molecule Gαq-biased GHSR1a agonist with binding IC50 of 1.3 uM.N8279 is nearly an order of magnitude (8.9-fold) more potent than the endogenous ligand ghrelin and is a full agonist.iCa2+ EC50 of N8279 is 41-fold more potent than its GHSR1a binding IC50, suggesting possible allosteric activity, which could be competitively inhibited by GHSR1a antagonists YIL781 and JMV2959.N8279 is a weak activator of GHSR1a-mediated, βarr2-dependent cellular responses relative to ghrelin.N8279 requires receptor sites and/or conformational states driven by the GHSR1a ECD that are distinct from ghrelin.N8279 is brain-penetrant and attenuates aberrant DAergic behavior in mice. |
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| DC70648 |
NH-23-C2
Featured
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NH-23-C2 (Caspase-2 inhibitor NH-23-C2) is a potent, selective and cell-permeable endogenous caspase-2 inhibitor, does not block caspase-3 or caspase-8.NH-23-C2 displays off-reactivity with cysteine and threonine proteases (cathepsins B, L, V, S).HCT116 cells were preincubated with NH-23-C2 inhibitor, MDM-2 cleavage was inhibited in a concentration-dependent manner (IC50 =3.11 μM).NH-23-C2 selectively block caspase-2 activity and caspase-2-mediated MDM-2 cleavage. |
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| DC70652 |
Nigratine
Featured
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Nigratine (6E11) is a highly specific, non-ATP competitive inhibitor of RIPK1 kinase (IC50=1.6 uM), inhibits necroptosis and ferroptosis.Nigratine inhibits necroptotic cell-death induced by TNF-α in Jurkat-Fadd def cells with IC50 of 4.6 uM.Nigratine is significantly more potent than the specific RIPK1 necroptosis inhibitor, Nec-1s.Nigratine (50 uM) strongly inhibits the ferroptotic cell death induced by excess of glutamate, erastin, and RSL3, in both murine HT22 and human SH-SY5Y cell lines, protects SH-SY5Y human neuroblastoma cell line from cell death triggered by both class I and II-inducers of ferroptosis.Nigratine protects porcine kidney epithelial LLC-PK1 cell line from lipid peroxidation and cell death triggered by RSL3.Nigratine protects human bronchial organoids from necroptosis and ferroptosis. |
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| DC70653 |
NJH-2-075
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NJH-2-075 is an alkyne-functionalized probe of EN523, retains binding to OTUB1 in vitro. |
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| DC70655 |
NLX-204
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NLX-204 is a potent and selective ERK1/2 phosphorylation-preferring serotonin 5 HT1A receptor agonist with pKi = 10.19. NLX-204 displayed high selectivity in the SafetyScreen44 panel (including hERG channel), high solubility, metabolic stability, and Caco-2 penetration and did not block CYP3A4, CYP2D6 isoenzymes, or P-glycoprotein. Preliminary in vivo studies confirmed its promising pharmacokinetic profile. NLX-204 also robustly stimulated ERK1/2 phosphorylation in rat cortex and showed highly potent (MED = 0.16 mg/kg) and efficacious antidepressant-like activity, totally eliminating immobility in the rat Porsolt test. |
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| DC70662 |
NPX-800
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NPX-800 is a potent, selective, oral heat shock factor 1 (HSF1) pathway inhibitor. |
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| DC70698 |
PK68
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PK68 (RIPK1 inhibitor PK68) is a potent necroptosis inhibitor seletively targeting RIPK1 kinase activity, potently inhibits TNF-induced necroptosis (EC50, 23 and 13 nM in human and mouse cells, respectively).PK68 blocks cellular activation of RIPK1, RIPK3, and MLKL upon necroptotic stimuli.PK68 is a type II inhibitor of RIP1 kinase, highly selective inhibitor of RIPK1 kinase activity with IC50 of 90 nM, does not affect RIPK3 kinase activity at 1 uM, also demonstrated a reasonable selectivity against a panel of 369 kinases.PK68 exhibits a favorable pharmacokinetic profile and no obvious toxicity in mice.PK68 ameliorates TNF-induced systemic inflammatory response syndrome, and displays preventive suppression of tumor metastasis in the mouse cancer models. |
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| DC70702 |
PLX8394
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PLX8394 (PLX-8394) is a next-generation, orally available, small-molecule BRAF inhibitor with IC50 values of 3.8 nM, 14 nM and 23 nM for BRAF (V600E), WT BRAF and CRAF, respectively.PLX8394 suppresses mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation, overcame several known mechanisms of resistance to first-generation RAF inhibitors.PLX8394 inhibits ERK signaling by specifically disrupting BRAF-containing dimers, including BRAF homodimers and BRAF-CRAF heterodimers, but not CRAF homodimers or ARAF-containing dimers.As a BRAF-specific dimer breaker, PLX8394 selectively inhibits ERK signaling in tumors driven by dimeric BRAF mutants, including BRAF fusions and splice variants as well as BRAF V600 monomers, but spares RAF function in normal cells in which CRAF homodimers can drive signaling. |
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| DC70705 |
PQR514
Featured
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PQR514 is a potent selective pan-PI3K inhibitor with binding Ki of 2.2 and 33 nM for p110α and mTOR, repectively.PQR514 inhibits phosphorylated S6 ribosomal protein (pS6, Ser235/236) and phosphorylation PKB Ser473 in A2058 cells with IC50 of 17 and 68 nM, respectively.PQR514 displays negligible interference with protein kinase activities at 10 uM in a KINOMEScan panel.PQR514 exhibits growth inhibition in vitro across a panel of 66 tumor cells with GI50 of 0.25 uM.PQR514 demonstrates significant antitumor activity aginst OVCAR-3 human ovarian cancer xenograft model in BALB/c nude mice. |
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| DC70708 |
Prinomastat
Featured
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Prinomastat (AG3340) is a potent, selective MMP inhibitor with pM affinities for inhibiting gelatinases (MMP-2 and -9, Ki=50-150 pM), MMP-14 and MMP-13; demonstrates broad antitumor activity in a number of tumor models, inhibits glioma invasion or growth of the human malignant glioma cell line U87; also suppresses tumor growth in a malignant glioma tumor model. |
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| DC70709 |
PRL-295
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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. |
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| DC70714 |
PSB-16671
Featured
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PSB-16671 is a novel orthosteric and allosteric activator of GPR84, activates human GPR84 with EC50 of 41.3 nM in cAMP accumulation assays.
PSB-16671 is selective versus related fatty acid receptors and the arylhydrocarbon receptor.
PSB-16671 shows an EC50 of 5.47 uM in β-Arrestin assays, and allosteric KB value of 634 nM. |
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| DC70722 |
Q308
Featured
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Q308 is a small molecule that silences the latent HIV-1 provirus by inhibiting Tat-mediated gene transcription and selectively downregulates the expression levels of the facilitated chromatin transcription (FACT) complex.Q308 induced the preferential apoptosis in HIV-1 latently infected cells, Q308 may reduce the size of the viral reservoir. |
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| DC70723 |
QC-01–175
Featured
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QC-01-175 is a hetero-bifunctional molecule designed to engage both tau and Cereblon (CRBN) to trigger tau ubiquitination and proteasomal degradation (tau PROTAC).QC-01–175 effected clearance of tau in frontotemporal dementia (FTD) patient-derived neuronal cell models, with minimal effect on tau from neurons of healthy controls.QC-01–175 also rescued stress vulnerability in FTD neurons, phenocopying CRISPR-mediated MAPT-knockout. |
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