CCX-6239 is a novel potent, orally available CCR4 inhibitor with potential utility in the treatment of allergic airways disease.

CCT369347 (CCT-369347) is potent selective inhibitor of BCL-6 with TR-FRET IC50 of 26 nM.CCT369347 demonstrated antiproliferative activity in a panel of BCL6-positive lymphoma cell lines (OCI-Ly1, SU-DHL-4, and SU-DHL-6) with IC50 of 1.68-3.45 uM, with weaker activity against low BCL6 expression cells and noncytotoxocity. CCT369347 inhibits BCL6 in a cellular assay with a submicromolar IC50 and shows promising early PK.

CCR7 inhibitor Cmp1205 is an allosteric ligand and antagonist for human CC chemokine receptor 7 (CCR7) with Kd of 3 nM, suppresses arrestin binding in response to activation by CCL19 with IC50 of 7.3 uM.Cmp1205 binds to a pocket at the intracellular part of CCR7 between the ends of TM1, TM2, TM3, and TM6 and the loop between TM7 and H8.Cmp1205 allosterically inhibits binding of the native chemokine CCL19 ligand in a membrane-based competition binding experiment with IC50 of 35 nM.

CCR2 inhibitor SD-24 is a potent selective CCR2 antagonist with pKi of 8.5.

CCR2 covalent-IN-14 is a covalent, negative allosteric modulator (NAM) of CCR2, binds to intracellularly pocket of CCR2 with Ki of 4 nM.CCR2 covalent-IN-14 is more potent than non-covalent analogue and wash-resistant in functional assays (IC50=33 nM in GTPγS binding assay on U2OS-CCR2 cell membranes, IC50=4 nM in β-arrestin recruitment assays).CCR2 covalent-IN-14 displays little to no inhibitory potency on CCR1 and CCR5.The affinity of CCR2 covalent-IN-14 for both the C70S and C75S CCR2 mutants is significantly decreased compared to WT CCR2.

CBS1194 is a novel specific fusion inhibitor for group 2 influenza viruses, inhibits IAVs bearing group 2 HAs (pseudo-H7, EC50=0.25 uM).CBS1194 displays no inhibition against both pseudo-H5 and pseudo-Lassa.CBS1194 exhibitss potency agianst group II influenza viruses influenza A/rhea/North Carolina/1993 (H7N1) and A/Hong Kong/1/1968 (H3N2) with EC59 of 3.17 and 1.60 uM, respectively.CBS1194 displays no inhibitory activity against group 1 influenza viruses, including A/Puerto Rico/8/1934 (H1N1) and A/Viet Nam/1203/04 (H5N1).CBS1194 acts at an early stage of viral infection, inhibits viral HA mediated hemolysis, and prevents the low pH-induced conformational change of HA.The substitutions K1172N and T301A but not D71N to confer resistance to CBS1194.

CBR417 (CBR-417) is a potent and selective antiwolbachial activity compound (Anti-Wolbachia wMel In vitro HCI cell-based assay IC50=21 nM, IC90=1640 nM).CBR417 demonstrates potent antiwolbachial activity was confirmed in L. sigmodontis, Brugia malayi, and Onchocerca ochengi in vivo preclinical models of filarial disease.CBR417 demonstrates in vitro selectivity against Loa loa (a safety concern in endemic areas).

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.

CBK006377 (CBK77) is a small molecule inhibitor of the ubiquitin-proteasome system (UPS) with EC50 of 4.3 uM in MelJuSo Ub-YFP cells (6h treatment).CBK77 (16h treatment, 10 uM) causes an irreversible, global impairment of the UPS collapse, accompanied by a general accumulation of ubiquitylated proteins and caspase-dependent cell death.CBK77 causes a global impairment of ubiquitin-dependent proteasomal degradation without global inhibition of proteasome or DUB activity.NAD(P)H:quinone oxidoreductase 1 (NQO1) is a critical factor for CBK77-mediated UPS impairment, CBK77 is an NQO1 substrate, efficiently metabolized by NQO1.CBK77 reduces growth of NQO1-proficient human cancer cells and xenograft tumors in mice without overt signs of toxicity.

CaNDY is a highly potent rectifier of the aberrant splicing, potently inhibits DYRK1A, DYRK1B, CLK1/CLK2/ with IC50 of 21.6/68.3/116 nM in in vitro kinase assays.CaNDY is a potent and selective inhibitor of DYRK family kinases, CaNDY induces selective degradation of DYRK1A, and inhibits catalytic activity of recombinant DYRK1A with IC50 value of 7.9 nM by competing with ATP, antagonizes the CDC37 interaction with DYRK1A.CaNDY demonstrated CFTR pseudo exon suppression with EC50 of 1.2 uM, 20.4 times lower than that of TG003.Splice modulation by CaNDY is mediated by its CLK-inhibition activity.CaNDY, but not CFTR modulator VX-809, rescues mature CFTR expression from the CFTR gene with the 3,849 + 10 kb C>T mutation, suppresses SRSF phosphorylation.CaNDY (3 uM) treatment rescued CFTR channel activity from CFTRC>T-GFP at an extent comparable to that of CFTRWT-GFP, demonstrating a restoration of functional CFTR expression.

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.

CAM833 (CAM-833) is a potent, specific chemical inhibitor of the RAD51-BRCA2 interaction and RAD51 oligomerization with Kd of 366 nM; CAM833 inhibited RAD51 foci formation 6 h after exposure to 3 Gy IR, in a concentration-dependent manner with an IC50 of 6 uM, causeed a concentration-dependent decrease in RAD51 foci accompanied by increased DNA damage in A549 cells. CAM833 inhibted RAD51 molecular clustering at DNA damage sites visualized by SMLM, suppressed homologous recombination and potentiated cell-cycle arrest. CAM833 potentiated the growth suppressive effect of PARP1 inhibition in BRCA2 wild-type cells, as well as dose-dependent growth inhibition when combined with ionizing radiation.

CAD204520 (CAD 204520) is a potent, specific, oral available inhibitor of SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) with IC50 of 0.34 uM; CAD204520 preferentially targets mutated over wild-type NOTCH1 proteins in T-All and MCL. CAD204520 preferentially inhibited the Ca2+-ATPase by reducing SERCA's ATP hydrolysis activity with an IC50=0.34 uM as compared to the Na+/K+-ATPase (IC50 8.30 uM) and the H+-ATPase. CAD204520 modulates Notch1 signaling, and preferentially inhibits NOTCH1 mutated cancers. CAD204520 suppresses NOTCH1-mutated leukemic cells in a T-ALL xenografted model without causing cardiac toxicity.

C67399 is a small molecule that blocks the integrin β1 binding site of TLN1, reduces the malignant behaviours of TNBC in vitro (MDA-MB-231 cell, IC50=2.0 uM).C67399 treatment significantly reduced the viability of BT549 cells.C67399 (2 uM) significantly reduced the expression of integrin β1, AKT, FAK, and phosphorylated FAK in MDA-MB-231 cells, while did not affect the expression of integrin β3.C67399 inhibited the binding of TLN1 to integrin β1 in MDA-MB-231 cells.C67399 (1.75 mg/kg) inhibited tumour growth and metastasis of MDA-MB-231 cells in mice, without causing obvious structural toxic changes.

C5 complement inhibitor 7 (C5-IN-7) is a potent, small-molecule inhibitor of C5 complement protein with serum assay IC50 of <5 nM (2% human serum complement inhibition).C5-IN-7 demonstrated excellent potency and good aqueous solubility, inhibited MAC deposition with IC50 of 1 uM in a complement inhibition assay using 50% human whole blood.The C5 triple mutants (C704R, V705I and N707H) were not inhibited by C5 complement protein inhibitor 7 up to 100 uM.C5 complement protein inhibitor 7 binds within the predicted pocket between the C5a and MG8 domains in close proximity to the C5 convertase cleavage site (R751-L752).

BY27 (BD2 inhibitor BY27) is a potent, highly selective BET BD2 inhibitor with Ki of 8.9/8.2/14.2 nM for BRD2/3/4-BD2 respectively.BY27 displays 38-fold selectivity for BRD2-BD2 over BRD2-BD1.BY27 showed good antitumor activity in the MV4-11 xenograft model with an improved in vivo tolerance in mice compared with I-BET762.

BX471 is a potent, selective, orally available CCR1 antagonist with Ki of 1 nM for hCCR1, displays 100 times less affinity for rat CCR1; shows 10,000-fold selectivity for CCR1 compared with 28 GPCRs (); displays CCR1 ligands MIP-1α, RANTES, and MCP-3 with high affinity (Ki=1-5.5 nM), inhibits a number of CCR1-mediated effects including Ca(2+) mobilization, increase in extracellular acidification rate, CD11b expression; effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis.

BVQ1814 (BVQ-1814) is a highly effective fluorescent probe targeting PDE10A with highly potent affinity (IC50=0.9 nM), >1000-fold subfamily selectivity.

Burkfloxacin (BFX) is a fluoroquinolone analog that potently inhibits growth of intracellular Burkholderia.Burkfloxacin is active against other gram-negative organisms in vitro, showing similar potency to the widely used fluoroquinolone, ciprofloxacin (Cip), against Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853.Burkfloxacin near-completely inhibits plaque formation by Bt and Bp at concentration of 0.5 uM.Burkfloxacin functions as a canonical fluoroquinolone by inhibiting the negative DNA supercoiling activity of E. coli DNA gyrase.Treatment with Burkfloxacin was significantly more effective than ceftazidime, the current antibiotic of choice, for improving survival and decreasing bacterial counts in major organs in a murine model of fulminant respiratory melioidosis.

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.

BT2 is a thermostable small-molecule inhibitor of vascular permeability and angiogenesis, interacts with MEK1 and inhibits ERK phosphorylation, FosB/ΔFosB, and VCAM-1 expression.BT2 blocks endothelial FosB/ΔFosB expression, proliferation, migration and wound repair after in vitro injury and network formation.BT2 also inhibited a range of other regulatory genes involved in cell proliferation, migration, angiogenesis, and inflammation including intercellular adhesion molecule-1 (ICAM-1), CXCL2, KLF5, Egr-1, and Fos.BT2 reduced retinal leakage in rats at least as effectively as aflibercept, a first-line therapy for nAMD/DR.

BSJ-04-122 is a potent, selective, covalent dual MKK4/7 inhibitor with IC50 of 4/181 nM, displays excellent kinome selectivity; BSJ-04-122 covalently targets a conserved cysteine (Cys247 for MKK4, and Cys261 for MKK7) located before the DFG motif. SJ-04-122 exhibits potent cellular target engagement and induces robust target-specific downstream effects. In breast cancer cell lines, BSJ-04-122 potently inhibited JNK phosphorylation, BSJ-04-122 significantly decreased levels of T183/Y185 pJNK at 5 uM, resulting in complete inhibition at 10 uM in MDA-MB-231 cells. The combination of the dual MKK4/7 inhibitor BSJ-04-122 with a selective, covalent JNK inhibitor (JNK-IN-8) demonstrated an enhanced antiproliferative activity against triple-negative breast cancer cells.

BRD8 inhibitor DN02 is a first-in-class selective and cellularly active probe for NuA4 factor BRD8 (BD1) with IC50 of 34 nM, no affinity for BRD8 {BD2}, CBP, and p300.

BRD4 D1 inhibitor 30 is a high-affinity, BRD4 D1-selective chemical probe with Kd of 18 nM, 500-fold selectivity against BRD2 D1 and BRD4 D2.BRD4 D1 inhibitor 30 down regulated inflammation, IL-8 and chemokine in cell based assays, but was unable to reduce c-Myc expression at low concentration in multiple myeloma cells.

BR-001 (BR001) is a potent, selective, allosteric inhibitor of EED subunit of PRC2 complex, disrupts EED-H3K27me3 interaction (IC50=4.5 nM).BR-001 directly binds to EED in the H3K27me3-binding pocket, BR-001 significantly increases the thermal stability of EED in thermal shift assay.BR-001 is selective for EED, has no activity against 371 wild-type kinases.BR-001 significantly reduced the cellular H3K27me3 level and also exhibited a strong antiproliferative effect in Karpas 422 cells.BR-001 inhibited proliferation of DLBCL cells and tumor growth, and upregulated target genes expression.BR-001 has potent antitumor efficacy in vivo, modulates immune response to suppress syngeneic CT26 colon tumor.

BPR1M97 is a dual-acting mu-opioid receptor (MOP) and nociceptin-orphanin FQ peptide (NOP) receptor agonist with Ki values of 1.8 and 4.2 nM, respectively.BPR1M97 elicited full agonist properties for all cell-based assays tested in MOP-expressing cells.BPR1M97 acted as a G protein-biased agonist for NOP.BPR1M97 initiated faster antinociceptive effects after subcutaneous injection and elicited better analgesia in cancer-induced pain than morphine.BPR1M97 caused less respiratory, cardiovascular, and gastrointestinal dysfunction, compared with morphine.

BMS-905 is a potent dual inhibitor of TLR7 and TLR8 with IC50 of 0.3 nM (TLR7, IL-6 inhibition in mouse blood), shows good selectivity against TLR9 and other TLR family members.

BMS-846372 (BMS846372) is a potent, selective, orally active CGRP receptor antagonist with Ki of 0.07 nM (hCGRP).BMS-846372 inhibited CGRP-stimulated cAMP production in SK-N-MC cells with IC50 of 0.22 nM, could completely inhibited CGRP-mediated elevation of cAMP.BMS-846372 showed exposure-dependent inhibition of CGRP-induced increases in marmoset facial blood flow upon subcutaneous (sc) dosing in hαCGRP-induced increases in facial blood flow model.

BMS-570520 is a potent, selective CCR3 antagonist with IC50 of 1.9 nM, inhibits eotaxin-induced chemotaxis with IC50 of 0.068 nM.BMS-570520 displays reduced inhibition on CYP2D6 (IC50=1300 nM) compared with DPC168 (IC50=30 nM), also possesses >100-fold selectivity over 5-HT2a, DAT and NET.BMS-570520 showed good activity in murine models of CCR3 antagonism and greater in vitro potency and in vivo in the mouse intranasal eotaxin challenge mode.

BLM inhibitor 2 is a specific inhibitor of BLM (Bloom syndrome protein) ATPase-coupled DNA helicase activity (IC50=2.2 uM) via the allosteric binding site.BLM inhibitor 2 displays high selectivity over members of the RecQ-helicase family in ATP-turnover assays, including recombinant helicase domains (HD) from human WRN, human RecQ5 or E. coli helicase UvrD, and human RecQ1.BLM inhibitor 2 is a non-competitive inhibitor, does not interfere with ATP-binding, unliker ML216.BLM inhibitor 2 inhibits production of the single-stranded DNA product in a dose-dependent manner (IC50=1.8 uM) via inhibition of the helicase activity of BLM-HD.BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates (BLM, WRN, RECQ1, RECQ4, and RECQ5 in humans).