| DC70224 |
Autoquin |
Autoquin is a novel autophagy inhibitor (IC50=0.56 uM) by indirect modulation of the activity of the lysosomal enzymes acid sphingomyelinase and acid ceramidase;
Autoquin showed a dose‐dependent inhibition of EGFP‐LC3 puncta after 3 hours upon autophagy induction by amino acid starvation in the primary screening assay.
Autoquin is a lysosomotropic compound that acts as a functional inhibitor of acid sphingomyelinase, increases lysosomal mass and sequesters Fe2+ to the lysosomes in MCF7 cells, causing an increase in lysosomal reactive oxygen species. |
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| DC70251 |
BI-4916 |
BI-4916 (BI-4916) is the prodrug of BI-4924, which is a potent, selective NADH/NAD+-competitive PHGDH inhibitor with IC50 of 2 nM. |
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| DC70252 |
BI-4924
Featured
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BI-4924 (BI 4924) is a potent, selective NADH/NAD+-competitive PHGDH inhibitor with IC50 of 2 nM.BI-4924 splays high selectivity against the majority of other dehydrogenase targets. |
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| DC70275 |
BTX306 |
BTX306 (BTX-306) is a novel protein homeostatic modulator, potently reduces levels of GSPT1, eRF1, CK1α, MCL-1, and c-MYC in myeloma cells, overcomes bortezomib and lenalidomide resistance.BTX306 is much more potently reduced human-derived myeloma cell line viability, with median inhibitory concentrations in the single nanomolar range versus micromolar values for lenalidomide or pomalidomide, and more potently activated caspases 3/8/9.BTX306 did not impact viability of murine hematopoietic cells in an in vivo model, demonstrating its specificity for human cereblon.BTX306 did show some reduced activity in lenalidomide-resistant cell line models but nonetheless retained its nanomolar potency in vitro, overcame bortezomib resistance, and was equipotent against otherwise isogenic cell line models with either wild-type or knockout TP53.BTX306 demonstrated strong activity against primary CD138-positive plasma cells, showed enhanced anti-proliferative activity in combination with bortezomib and dexamethasone.BTX306 was effective in an in vivo systemic model of multiple myeloma. |
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| DC70284 |
CaMK1D-IN-18 |
CaMK1D-IN-18 is a potent, selective CaMK1D inhibitor with IC50 of 31 nM, >150-fold greater activity against CaMK1D than all non-CaMK1 kinases.CaMK1D-IN-18 improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration. |
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| DC70287 |
CBK288679 |
CBK288679 (CBK79) is a novel compound that impairs both protein degradation by the ubiquitin-proteasome system (UPS) and autophagy.CBK79 inhibits cell viability of MelJuSo Ub-YFP cells with 72h IC50 of 0.22 uM, CBK79-inflicted cell death was caspase-independent.CBK79 causes accumulation of ubiquitin-dependent and -independent proteasome substrates.CBK79 induces non-canonical lipidation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) that requires ATG16L1 but is independent of the ULK1 and class III phosphatidylinositol 3-kinase (PtdIns3K) complexes.CBK79 (10 uM) induces proteotoxic stress and the heat shock response in HOS GFP-LC3B cells.CBK79 has unique features as it inhibits both ubiquitin-dependent and -independent degradation of short-lived proteins by the UPS, as well as the degradation of long-lived proteins by autophagy. |
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| DC70302 |
CFT-14441 |
CFT-14441 is a potent and selective BRD9 BiDAC degrader with DC50 of 39 nM (2h), high selectivity over BRD4 abd BRD7.CFT-14441 efficiently degrades endogenous BRD9 in the Yamato-SS synovial sarcoma cell line, results in growth inhibition of BAF-perturbed HSSYII synovial sarcoma cells but not BAF-wild type SW982 soft tissue sarcoma cells.CFT-14441 demonstrates efficacy in both cell-derived and patient-derived models of synovial sarcoma (IV or IP dosing). |
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| DC70304 |
CFT8634
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CFT-8634 (CFT8634) is a potent, selective, orally bioavailable BRD9 BiDAC degrader with DC50 of 3 nM, high selectivity over BRD4 abd BRD7.Unlike BRD9 inhibition, BRD9 degradation is efficacious in preclinical models of synovial sarcoma and CFT8634 is ongoing for the treatment of SMARCB1-perturbed cancers. |
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| DC70305 |
CG428
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CG428 (CG-428) is a first-in-class potent and selective TRK degrader (PROTAC) with DC50 of 0.36 nM.CG428 (CG-428) showed selectivity for the degradation of endogenous TPM3-TRKA over ectopically expressed ATP/GTP binding protein-like 4 (AGBL4)-TRKB or ETS variant transcription factor 6 (ETV6)-TRKC fusion proteins in KM12 cells.CG428 exhibited higher potency for inhibiting growth of KM12 cells with IC50 of 2.9 nM, compared with the parental TRK kinase inhibitor.CG428 (CG-428) is a valuable chemical tool compound for investigating the in vivo function of TRK fusion during tumorigenesis |
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| DC70325 |
CS640 |
CS640 (CS-640) is a potent, selective CaMK1D inhibitor with nanomolar range at both the enzymatic and cellular levels.CS640 prevent Aβ induced tau hyperphosphorylation in culture, but were not able to protect cells from Aβ induced toxicity.CS640 was able to ablate Aβ induced increased tau phosphorylation at Thr181 in mouse primary neurons. |
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| DC70331 |
CU7218 |
CU7218 is a small-molecule inhibitor of 14-3-3 protein, inhibits the interaction between 9J10 and 14-3-3, displaces FOXO3a and other substrate proteins from 14-3-3 and reproduces the cellular phenotypes induced by 9J10 expression. |
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| DC70339 |
dBRD9 dihydrochloride
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dBRD9 dihydrochloride is a potent and selective degrader (PROTAC) of BRD9 with IC50 of 56.6 nM in MOLM-13 cells.dBRD9 is composed of the BRD9 inhibitor BI 7273 conjugated to the cereblon E3 ligase ligand pomalidomide.dBRD9 does not degrade BRD4 or BRD7 at concentrations up to 5 uM.dBRD9 exhibits antiproliferative effects in human AML cell lines. |
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| DC70340 |
dBRD9‐A |
dBRD9‐A is a chemical degrader (PROTAC) of BRD9, a highly specific binder of the BRD9 bromodomain and elicits near complete BRD9 degradation at low nanomolar concentrations.dBRD9‐A blocks synovial sarcoma tumour progression and oncogenic transcription.dBRD9‐A limited IFN‐induced expression of certain ISGs in multiple cell types, significantly reduced induction of 29 ISGs, including many ISGs known to harbor antiviral activity against the viruses, such as MX1, MX2, IFITM1, IFITM3, IDO1, and BST2. |
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| DC70348 |
DDC-01-163 |
DDC-01-163 is an allosteric EGFR degrader that selectively inhibit the proliferation of L858R/T790M (L/T) mutant Ba/F3 cells while leaving wildtype EGFR Ba/F3 cells unaffected;
DDC-01-163 exhibited an acceptable biochemical potency with an IC50 value of 45 nM against EGFR L858R/T790M.
DDC-01-163 is also effective against osimertinib-resistant cells with L/T/C797S and L/T/L718Q EGFR mutations.
The anti-proliferative activity of DDC-01-163 against L858R/T790M EGFR-Ba/F3 cells is enhanced when combined with an ATP-site EGFR inhibitor, Osimertinib. |
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| DC70353 |
DGY-09-192 |
DGY-09-192 is a bivalent degrader (PROTAC) that couples the pan-FGFR inhibitor BGJ398 to a CRL2VHL E3 ligase recruiting ligand,preferentially induces FGFR1/2 degradation while largely sparing FGFR3/4.DGY-09-192 exhibited two-digit nanomolar DC50s for both wildtype FGFR2 and several FGFR2-fusions, resulting in degradation-dependent antiproliferative activity in representative gastric cancer and cholangiocarcinoma cells (IC50=1 nM).DGY-09-192 induced degradation of a clinically relevant FGFR2 fusion protein in xenograft model. |
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| DC70387 |
Endosidin 9 |
Endosidin 9 (ES9) is a novel mitochondrial uncoupler, and a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems, strongly reduces FM4-64 uptake in Arabidopsis root cells with IC50 of 5 uM.Endosidin 9 (ES9) inhibits CME dynamics and organelle movement in the cytoplasm.Endosidin9 (ES9) inhibits clathrin-mediated endocytosis largely through cytoplasmic acidification. |
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| DC70409 |
FGIN-1-27
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FGIN-1-27 is an anxiolytic compound that acts as a selective agonist at the peripheral benzodiazepine receptor (TSPO).FGIN-1-27 inhibited Th17 cell differentiation, significantly downregulated the expression of RORγt target genes, notably Il17a, Il17f, Il23r, Ltb4r1,Ccr6.FGIN-1-27 protected mice against EAE, induced amino acid starvation response (AAR), FGIN-1-27 produced anti-anxiety and anti-panic effects in non-mammalian models. |
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| DC70442 |
GRK6 inhibitor 18
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GRK6 inhibitor 18 is a potent, and selective GRK6 inhibitor with IC50 of 8 nM.GRK6 inhibitor 18 displays >1,000-fold selectivity over Aurora A, as well as high selectivity against a panel of 85 kinases.GRK6 inhibitor 18 has potent cellular target engagement and antiproliferative activity against MM cells (IC50=0.4-0.46 uM) and is synergistic with bortezomib. |
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| DC70444 |
GS-680
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GS-680 (GS680) is a novel selective and ATP-competitive CaMKII inhibitor with biochemical IC50 of 2.3 and 15.9 nM against CaMKIIδ and CaMKIIα, respectively.GS-680 inhibited phospholamban phosphorylation in NRVM with an EC50 of 98.9 nM.GS-680 inhibits premature atrial contractions.GS-680 significantly reduced CaMKII autophosphorylation.GS-680 inhibits pro-arrhythmic activity in human atrium and improves contractility in failing human ventricle. |
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| DC70479 |
HDAC6 Degrader 13f
Featured
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HDAC6 Degrader 13f (YZ268) is a selective HDAC6 degrader (PROTAC) with high potency, specific chemical probe to knock-down HDAC6. |
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| DC70480 |
HDAC8 PROTAC 1 |
HDAC8 PROTAC 1 is a first-in-class proteolysis targeting chimera (PROTAC) for selective degradation of histone deacetylase 8 (HDAC8).HDAC8 PROTAC 1 induced degradation of HDAC8 without affecting the levels of other HDACs in cellular assays, and inhibited the growth of T-cell leukemia Jurkat cells more potently than a conventional HDAC8 inhibitor. |
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| DC70497 |
HTT-D3
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HTT-D3 is a potent, CNS-penetrant, orally bioavailable huntingtin (HTT) splicing modulator, affects HTT pre-mRNA splicing and reduces HTT expression with IC50 of 8 nM.Oral administration of HTT-D3 resulted in dose-dependent and approximately equivalent mHTT protein lowering in both brain and peripheral tissues in mouse models carrying human mHTT transgene, BACHD and Hu97/18.HTT-D3 (10 mg/kg) reduced mHTT mRNA and protein levels in BACHD brain in BACHD mice. |
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| DC70499 |
HuR inhibitor KH-3
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HuR inhibitor KH-3 is a small molecule, selective inhibitior of HuR function with Ki of 0.83 and 0.72 uM in FP and AlphaLISA assays, respectively.KH-3 potently inhibits breast cancer cell growth in vitro and in vivo.KH-3 inhibits breast cancer cell invasion in vitro as well as delays initiation of lung colonies and improves mouse survival in an experimental metastasis model in vivo.KH-3 suppresses breast cancer cell invasion by disrupting HuR-FOXQ1 mRNA interaction.Inhibition of HuR with KH-3 yielded a significant reduced in the progression of pathological cardiac hypertrophy in a transverse aortic constriction model. |
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| DC70533 |
K-312 |
K-312 is a novel cholesteryl ester transfer protein (CETP) inhibitor with IC50 of 60 nM, also suppresses hepatocyte expression of PCSK9, raises HDL and lowers LDL cholesterol levels in vivo; raises HDL cholesterol, decreases LDL cholesterol, and attenuates aortic atherosclerosis in cholesterol-fed rabbits; decreases PCSK9 expression in human primary hepatocytes and in the human hepatoma cell line HepG2, decreases the occupancy of SREBP-1 and SREBP-2 on the sterol regulatory element of the PCSK9 promoter. |
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| DC70560 |
LCC03 |
LCC03 is a salicylanilide derivative and autophagy inducer, dose-dependently suppresses proliferation and retarded cell-cycle progression in CRPC cells (IC50, 0.69 to 4.8 uM).The classical autophagy features, including autophagosome formation and LC3-II conversion, were dramatically shown in LCC03-treated CRPC cells, which was associated with the suppressed AKT/mTOR signaling pathways, a major negative regulator of autophagy.LCC03 also showed an expanded morphology of the endoplasmic reticulum (ER), increased expression of the ER stress markers GRP78 and PERK, and eIF2α phosphorylation.The PERK-eIF2α pathway contributed to the LCC03-induced autophagy.LCC03 suppressed the growth of CRPC xenografts in mouse bone without systemic toxicity in tumor-bearing mice. |
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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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| 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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| DC70619 |
MS910 |
MS910 (MS-910) is the first CRBN-recruiting MEK1/2 degrader (PROTC) with HT29 DC50 of 118/55 nM for MEK1/2 degradation, respectively.MS910 displays antiproliferation potency against HT29 cell with GI50 of 330 nM, degrade MEK1 and MEK2 and inhibit pERK signaling in a time-dependent manner. |
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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
Featured
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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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