| 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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| DC70727 |
RA306
Featured
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RA306 (RA-306) is a selective, potent, orally active, ATP-competitive CaMKII inhibitor, inhibits CaMKII delta (IC50=15 nM), gamma (IC50=25 nM), and alpha (IC50=61 nM) isoforms.RA306 displays a good selectivity profile vs. kinases and non-kinase targets, as compared with KN-93.RA306 also displays a good cellular activity in cardiomyocytes from human, rat, and mice, with IC50s in the 200 nM range.Isoproterenol-induced phosphorylation of Thr17-PLN, normalized to total PLN, was fully inhibited by RA306 in a dose-dependent manner, with IC50s of 140 nM in rat, 205 nM in mouse, and 220 nM in human cardiomyocytes. |
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| DC70728 |
RA608
Featured
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RA608 (RA-608) is a potent, selective, ATP-competitive, orally available CaMKII inhibitor, inhibits human CaMKIIδ, CaMKIIγ, CaMKIIα, and CaMKIIβ with IC50 of 22, 51, 121, and 1135 nM, respectively.RA608 displays a good selectivity profile against a broad panel of 304 human recombinant kinases.RA608 significantly reduces SR Ca leak in human atrial cardiomyocytes, reduces diastolic tension of human atrial trabeculae, does not affect action potential characteristics; attenuates heart failure in the murine HF model induced by TAC. |
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| DC70765 |
SD-36
Featured
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SD-36 (STAT3 degrader SD-36) is a potent, selective STAT3 degrader (PROTAC), potently induces the degradation of STAT3 protein in vitro and in vivo.SD-36 is designed using an analogue of CRBN ligand lenalidomide and the STAT3 inhibitor SI-109, binds to recombinant STAT3 protein with Ki of 11 nM.SD-36 (250 nM) depleted >90% of STAT3 protein in MOLM-16 cells after 4 hr treatment and >50% of STAT3 protein in DEL, KI-JK and SU-DHL-1 cells after 7 hr treatment, also efficiently degraded STAT3 protein in murine cells.SD-36 displays extremely high cellular selectivity for degradation of STAT3 over other STATs.SD-36 effectively degrades both wild-type and mutated STAT3 proteins in cells, effectively degrades mutated STAT3 (D661Y, K658R mutant), also effectively degrades CRISPR-mutated homozygous Y705F mutant STAT3 protein in DLD-1/STAT3Y705F/Y705F cells.SD-36 displayed strong growth-inhibitory activities in a subset of leukemia and lymphoma cell lines (MOLM-16 cell line IC50, 35 nM), 100-fold more potent than SI-109.SD-36 (i.v. 25 mg/kg) effectively and selectively depletes STAT3 protein, achieves complete and long-lasting tumor regression in in mouse xenograft tumors. |
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| DC70775 |
SHP2 PROTAC R1-5C |
SHP2 PROTAC R1-5C is a potent and highly selective SHP2 PROTAC created by conjugating RMC-4550 with pomalidomide using a PEG linker, with a low nanomolar DC50;
SHP2 PROTAC R1-5C is highly selective for SHP2, induces degradation of SHP2 in leukemic cells at submicromolar concentrations.
SHP2 PROTAC R1-5C inhibits MAPK signaling, and suppresses cancer cell growth.
SHP2 PROTACs serve as an alternative strategy for targeting ERK-dependent cancers and are useful tools alongside allosteric inhibitors for dissecting the mechanisms by which SHP2 exerts its oncogenic activity. |
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| DC70788 |
SMN2 splicing modulator TEC-1
Featured
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SMN2 splicing modulator TEC-1 is a novel specific, CNS penetrant small molecule SMN2 splicing modulator, increases the expression level of FL-SMN2 mRNA and decreases the expression level of Δ7 mRNA.TEC-1 showed higher selectively (>60-fold) on galactosylceramidase and huntingtin gene expression compared to previously reported compounds (e.g., SMN-C3) due to off-target effects on cryptic exon inclusion and nonsense-mediated mRNA decay.TEC-1 modulates SMN2 splicing and displays disease-modifying effects in motor neurons derived from SMA patient iPSCs (GM24468).|TEC-1 rescues the phenotype in a murine model of spinal muscular atrophy (SMA). |
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| DC70791 |
STING PROTAC SP23 |
SP23 is a STING protein degrader (PROTAC) based on a small-molecule STING inhibitor (C-170) and pomalidomide (a CRBN ligand), shows degradation potency with DC50 of 3.2 uM.SP23 exerted high anti-inflammatory efficacy in a cisplatin-induced acute kidney injury mouse model by modulating the STING signaling pathway. |
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| DC70818 |
SY2-062 |
SY2-062 is a thalidomide derivative and useful precursor for synthesis of thalidomide-based PROTAC degrader. |
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| DC70841 |
Thailanstatin B |
Thailanstatin B is a potent antiproliferative natural product and pre-mRNA splicing inhibitor, potential antibody-drug conjugate payload. |
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| DC70842 |
Thailanstatin D |
Thailanstatin D (TST-D) is a potent antiproliferative natural product and direct precursor of Thailanstatin A, inhibits eukaryotic RNA splicing with stiong anti-tumor activities.Thailanstatin D inhibit AR-V7 gene splicing by interfering the interaction between U2AF65 and SAP155 and Thailanstatin D preventing them from binding to polypyrimidine tract located between the branch point and the 3' splice site.Thailanstatin D exhibits a potent tumor inhibitory effect on human CRPC xenografts leading to cell apoptosis.Thailanstatins are attractive cytotoxin agent for ADC design. |
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| DC70847 |
TIM-063 |
TIM-063 (TIM063) is a potent, selective, ATP-competitive CaMKK inhibitor with Ki of 0.35/0.2 uM for CaMKKα and CaMKKβ, respectively.TIM-063 directly targets the catalytic domain of CaMKK, similar to STO-609.TIM-063 suppressed the ionomycin-induced phosphorylation of exogenously expressed CaMKI, CaMKIV, and endogenous AMPKα in HeLa cells with an IC50 of 0.3 uM.TIM-063 suppressed CaMKK isoform-mediated CaMKIV phosphorylation in transfected COS-7 cells.TIM-063 displayed cell permeability and the ability to inhibit CaMKK activity in cells. TIM-063 is a useful chemical probe for the precise analysis of CaMKK-mediated signaling pathways. |
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| DC70864 |
UHMCP1 |
UHMCP1 is a small molecule that prevents the SF3b155/U2AF65 interaction, binds to the hydrophobic pocket of the U2AF65 UHM domain (Kd=1-20 uM), impacts splicing and cell viability. |
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| DC70901 |
Wbox2 |
Wbox2 is a membrane-permeant peptide that potently inhibits clathrin-mediated endocytosis (CME, IC50=3 uM), binds to SNX9 and AP2 and perturbs clathrin interactions with AP2 and SNX9.Wbox2 has no effect on cell viability at ≤30 uM and exhibited an IC50 for cytotoxicity (>40 uM) that is 10-fold higher than that needed to inhibit CME.Wbox2 interferes with AP2–clathrin interactions and alters CCP dynamics, binds to both AP2 and SNX9 with binding affinities of 4.0 and 26.2 uM. |
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| DC70915 |
YOK-1304 AUTOTAC intermidate 1 |
YOK-1304 AUTOTAC intermidate 1 is an intermidate for AUTOTAC design. |
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| DC70916 |
p62-ZZ ligand YOK-1304 |
YOK-1304 is a small molecule p62-ZZ domain ligand, activate p62-dependent selective macroautophag, used for AUTOTAC design.AUTOphagy-TArgeting Chimera (AUTOTAC) is a general chemical tool and platform technology, which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands.AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated into oligomeric bodies in complex with targets for their sequestration and degradation. |
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| DC70917 |
p62-ZZ ligand YOK-2204 |
YOK-2204 is a small molecule p62-ZZ domain ligand, activate p62-dependent selective macroautophag, used for AUTOTAC design. |
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| DC70918 |
YOK-2204 linker conjugate 1 |
YOK-2204 linker conjugate 1 is a PEG linker added to p62-ZZ ligand YOK-2204 for AUTOTAC design. |
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| DC70920 |
p62-ZZ ligand YTK-105 |
YTK-105 is a small molecule p62-ZZ domain ligand, activate p62-dependent selective macroautophag, used for AUTOTAC design. |
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| DC70921 |
YTK-105 linker conjugate 1 |
YTK-105 linker conjugate 1 is a PEG linker added to p62-ZZ ligand YTK-105 for AUTOTAC design. |
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| DC70923 |
YX-2-107
Featured
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YX-2-107 is a CRBN-recruiting and specific CDK6-degrading PROTAC with IC50 of 0.69 and 4.4 nM for CDK4 and CDK6 in vitro, selectively degardes CDK6 in Ph+ BV173 ALL cells with a degradation constant of 4 nM.YX-2-107 does not affect expression of IKZF1 and IKZF3, and does not degarde CDK4 protein.YX-2-107 inhibits S-phase entry, cell proliferation, RB phosphorylation, and FOXM1 expression and induces the selective degradation of CDK6 in Ph+ BV173 and SUP-B15 cells.|PROTAC YX-2-107 is bioavailable in mice and pharmacologically active in suppressing Ph+ ALL proliferation in a mouse xenograft of Ph+ ALL, comparable or superior to that of the CDK4/6 enzymatic inhibitor palbociclib. |
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| DC70924 |
YX-2-115 |
YX-2-115 is a palbociclib derivative compound with piperazine-linker tail for PROTAC YX-2-107 synthesis, inhibits CDK6 with IC50 of 4.5 nM. |
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| DC70925 |
YX-A-1 |
YX-A-1 is a small-molecule modulator of human islet amyloid polypeptide (hIAPP) assembly, specifically enhances amyloid formation;
YX-A-1 accelerates wt hIAPP assembly, even when added in substoichiometric concentration ratios (e.g. at a peptide:YX-A-1 molar ratio of 1:0.5 the t50 is reduced ~1.5-fold).
YX-A-1 is a useful chemical tools to study hIAPP aggregation. |
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| DC70926 |
YX-I-1 |
YX-I-1 is a small-molecule modulator of human islet amyloid polypeptide (hIAPP) assembly, specifically inhibits amyloid formation;
YX-I-1 inhibits the aggregation of wt hIAPP, extending the t50 from 15.1 ± 0.2 h to 23.4 ± 1.0 h at a 1:7 molar ratio of peptide:inhibitor.
YX-I-1 inhibits primary nucleation, secondary nucleation and elongation of wt hIAP.
YX-A-1 is a useful chemical tools to study hIAPP aggregation. |
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| DC70202 |
ARN22089 |
ARN22089 (ARN 22089) is a specific small molecule inhibitor of putative CDC42 family effector interaction, binds to CDC42 and has broad anti-cancer activity and inhibits MAPK and S6 signaling.ARN22089 could inhibit CDC42-PAK interactions with EC50 of 0.1 uM, and inhibit RHOJ/PAK interactions with approximate EC50 of 1-5 uM.ARN22089 has a single-digit micromolar IC50 activity against sensitive cell lines (WM3248, SKMel3, A375, and SW480), has IC50 of < 10 uM for 55/100 cell lines in a panel of 100 cancer cell lines with various different mutations, including several cell lines with neuroblastoma RAS (NRAS) mutations.ARN22089 inhibits MAPK and S6 phosphorylation and influences NFkB signaling in vitro.ARN22089 specifically inhibits tumor angiogenesis in 3D vascularized microtumors, shows drug-like properties and inhibits tumor growth in vivo.ARN22089 selectively binds and inhibits CDC42 effector interactions.ARN22089 binds better to the purified CDC42 compared with other known CDC42 inhibitors (ZCL278, ML141, R-ketoralac, and Casin).CDC42 family GTPases (RHOJ, RHOQ, CDC42) are linked to multiple human cancers and modulate cell-cycle progression, tumor cell migration/invasion, and tumor angiogenesis. |
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| DC70944 |
H-Tyr(SO2F)-OMe-18F |
H-Tyr(SO2F)-OMe-18F, a 18F-fluorosulfurylated phenol, is a positron emission tomography (PET) tracer. |
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| DC70946 |
Colibactin |
Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. Colibactin has the potential for the research of colorectal cancer. |
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| DC70956 |
Tropatepine |
Tropatepine is an orally active, anticholinergic muscarinic antagonist and can be used as an antiparkinsonian agent. Tropatepine is used to combat against extrapyramidal syndrome induced by neuroleptic drugs. |
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| DC70957 |
(+)-3-Carene |
(+)-3-Carene, a bicyclic monoterpene, is one of the major components of the pine tree essential oils. (+)-3-Carene is a (+)-enantiomer of 3-Carene. |
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| DC70960 |
Azapropazone |
Azapropazone is a nonsteroidal anti-inflammatory drug (NSAID). Azapropazone can be used for the research of rheumatoid arthritis and other rheumatoid conditions. |
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| DC70961 |
Azintamide |
Azintamide (Bilipurum) can be used for the research of psoriasis vulgaris, dyspepsia and other conditions. |
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