MRTX-EX185 (EX185) is a novel potent small-molecule inhibitor of KRAS mutants, exhibits target engagement against KRAS(G12D) with IC50 of 90 nM, binds to GDP-loaded KRAS and KRAS(G12D), as well as the active GNP state.MRTX-EX185 also bound GDP-loaded HRAS.MRTX-EX185 engages both nucleotide states-albeit with preference for the inactive GDP-loaded protein-and might present an opportunity to inhibit even constitutively active (GTP-loaded) KRAS hotspot mutants MRTX-EX185 engages numerous KRAS Q61, G12 and G13 mutant proteins and drives antiproliferation.

MO-I-500 is a pharmacological inhibitor of m6A demethylase FTO, inhibits purified FTO demethylase catalyzing demethylation with IC50 of 8.7 uM.MO-I-500 treated cells exhibited a global increase in RNA methylation.HeLa cells treated with 25 μM MO-I-500 for 24 hours showed a 9.3% increase in N6-methyl-adenosine content in total RNA.MO-I-500 treatment caused a dramatic (>95%) inhibition in colony formation in SUM149-Luc cells.MO-I-500 modulates various microRNA in treated (25uM) HeLa cells.MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells, with relatively little effect on cell growth.MO-I-500 can strongly reduce the adverse effects of streptozotocin (STZ) model of AD in human astrocytoma CCF-STTG1 cells.

MMV688844 (MMV844) is a piperidine-4-carboxamide with bactericidal properties against M. abscessus, targets mycobacterial DNA gyrase.

MMV688533 is a potent antimalarial compound that displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials, MMV688533 is highly potent against multiple P. falciparum strains with IC50 values in low nanomolar range (P. falciparum 3D7, IC50=1.9 nM).MMV688533 also showed excellent ex vivo activity against asexual blood-stage parasites from fresh P. falciparum isolates (median IC50=1.3 nM, range=0.02 to 6.3 nM).MMV688533 remained potent in ex vivo assays against both P. falciparum and P. vivax with IC50 of 18.9 and 12.0 nM respectively.MMV688533 displayed fast and potent in vivo efficacy and favorable in vitro absorption, distribution, metabolism, and excretion and in vivo pharmacokinetic properties.MMV688533 antiplasmodial activity is unrelated to existing antimalarials and selects for low-grade resistance mediated in part by mutations in PfACG1 and PfEHD.

MMV675968 is a potent, small molecule inhibitor of Toxoplasma gondii (T. gondii) with IC50 of 0.02 uM, via the pathogen box.MMV675968 has been shown to be efficient against the planktonic form of C. albicans.MMV675968 showed an antiplasmodial activity against P. falciparum.MMV675968inhibited the growth of all four A. baumannii test strains with IC50 of 0.6-2.7 uM, IC90 of 0.7-3.9 uM, and MIC of 1.6-10 uM.

MMV084978 (MMV 084978) is an antiplasmodial drug-like compound tageting Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS), directly and selectively inhibit PfAcAS activity in vitro with IC50 of 370 nM.MMV084978 directly inhibits PfAcAS by preventing CoA and acetate binding.MMV084978 demonstrated in vitro efficacy (P. falciparum Dd2 EC50=150 nM) with increased liver-stage potency (Pbluc EC50= 520 nM).MMV084978 directly and selectively inhibit PfAcAS activity in vitro.

MMV019721 (MMV019721) is an antiplasmodial drug-like compound tageting Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS), directly and selectively inhibit PfAcAS activity in vitro with IC50 of 73 nM.MMV019721 directly inhibits PfAcAS by preventing CoA binding.MMV019721 has activity against blood-stage parasites in vitro (P. falciparum 3D7, EC50=460 nM) and against liver-stage P. berghei parasites (Pbluc EC50=2,000 nM).MMV019721 directly and selectively inhibits PfAcAS activity in vitro.

MMP-13i is a potent, highly-selective inhibitor of MMP-13 catalytic activity with IC50 of 2.7 nM, no inhibitory effect against MMP1/2/8/9/14 (IC50>5,000 nM).MMP-13i potently suppressed wild-type osteoclast formation in vitro at concentrations <100 nM.MMP-13i strongly inhibited multiple myeloma viability.MMP-13i treatment delayed multiple myeloma growth in immunocompetent syngeneic mouse model of multiple myeloma, inhibited multiple myeloma promotes systemic skeletal bone disease.

ML381 (VU0488130) is a highly mAChR subtype selective M5 orthosteric antagonist with IC50/Ki of 450/340 nM for hM5, has no inhibitory activity on hM1-4 (IC50>30 uM); exhibits good DMPK properties and CNS penetration (B:P ratio of 0.58) to support both in vitro and in vivo studies.

ML2-SA1 is a potent, selective and efficacious activator (agonist) of TRPML2 with EC50 of 1.24 uM and 2.38 uM for human and mouse TRPML2, respectively.ML2-SA1 displays high selectivity for TRPML2 and no significant activity at the related TRPML1 and TRPML3 channels.ML2-SA1 directly stimulates release of the chemokine CCL2 from macrophages, also stimulates macrophage migration, thus mimicking CCL2 function.

ML204 is a potent, selective antagonist of TRPC4 and TRPC5 channels, inhibits TRPC4β-mediated intracellular Ca(2+) rise with IC50 of 0.96 uM, exhibits 19-fold selectivity against TRPC6 channel; blocks TRPC4β currents activated through either μ-opioid receptor stimulation (50 nm DAMGO, IC50=3.55 uM) or intracellular dialysis of GTPγS (IC50=2.85 uM); shows no appreciable block by 10-20 uM for TRPV1, TRPV3, TRPA1, and TRPM8, as well as KCNQ2 and Nav Channels; also inhibits TRPC5 channel currents activated through co-stimulation of Gi/o and Gq/11 signaling by μ-opioid and M3-like muscarinic receptors.

MK-8666 is a selective partial GPR40 agonist developed for the treatment of type 2 diabetes mellitus.

MJM-1 is a small-molecule brain-penetrant HDAC inhibitor that increases the overall level of histone 3 (H3) acetylation in prostate cancer cell line.MJM-1 injected intraperitoneally (i.p.) crossed the BBB in mice and could be detected in the hippocampus, a brain region that mediates memory.MJM-1 (post-training i.p. administration) enhanced hippocampus-dependent spatial memory consolidation in male mice.

MINA53 inhibitor 9 is a first in class, potent, selective MINA53 inhibitor with IC50 of 1.6 uM, selective over NO66, KDM4-6 and other JmjC oxygenases.

Microtubule inhibitor PP-13 is a novel microtubule-destabilizing agent, directly inhibits microtubule assembly by targeting the colchicine-binding site in β-tubulin.PP-13 inhibits the growth of a wide range of cancer cell types, including targeted therapy-resistant and multidrug-resistant (MDR) cell lines (IC50=76-255 nM).PP-13 overcomes the multidrug-resistant (MDR) phenotype in cancer cells, induces mitotic blockade in cancer cells, interferes with both mitotic microtubule organization and spindle pole integrity.PP-13 induces cell prometaphase arrest then asymmetric division or direct apoptotic death.PP-13 reduces tumour growth and metastasis invasion in vivo.

MGB-BP-3 is a potent bactericidal antibiotic with a completely novel mode of action, selectively binds to the minor grove of microbial DNA, has the potential for Clostridioides difficile infection (CDI).

MEK4 inhibitor 6ff is potent, selective MEK4 inhibitor with IC50 of 66 nM.MEK4 inhibitor 6ff displays excellent selectivity across the entire MEK family, 150-fold more potent against MEK4 than any other MEKkinase, and is at least 385-fold selective against three other MEK kinases.

MEK4 inhibitor 15o is potent, selective, cell permeable MEK4 inhibitor with IC50 of 83 nM.MEK4 inhibitor 10e demonstrated significant reduction of phospho-JNK and antiproliferative properties against pancreatic cancer cell lines, molecular inhibition of MEK4 pathway activates the MEK1/2 pathway.MEK4 inhibitor 10e demonstrated synergistic effects against pancreatic cancer cells with the combination of MEK1/2 inhibitors.

MCB 3681 is a quinolonyl-oxazolidinone bactericidal antibiotic, has activity in vitro against Gram-positive bacteria. MCB3681 has a potent in vitro activity against C. difficile with MIC90 of 0.064 ug/ml.

MC-100093 (MC100093) is a potent, orally bioavailable upregulator of GLT-1 and devoid of antimicrobial properties.MC-100093 enhanced uptake of glutamate into astrocytes in a mouse neuron/astrocyte co-culture model with IC50 of 0.1 uM.MC-100093 restored the expression of NA core GLT-1.MC-100093 (50 mg/kg) attenuated cue-primed relapse to cocaine-seeking without reducing motivation to consume regular chow or sucrose pellets or affecting body weight.

MB 07811 (MB07811) is an orally bioavailable, liver-targeted prodrug of MB07344, which is a thyroid hormone receptor-beta agonist (TRβ) agonist, efficiently converted to MB07344 by liver microsomes in vivo; reduces cholesterol and both serum and hepatic triglycerides at doses devoid of effects on body weight, glycemia, and the THA.

M4K2234 is a potent, selective ALK1 (ACVRL1) and ALK2 (ACVR1) protein kinase inhibitor with IC50 of 7 and 14 nM, respectively.M4K2234 inhibits only ALK1/2 and one additional off target (TNIK) by kinome-wide screening against 375 protein kinases at 1 uM.M4K2234 demonstrated in cell based target engagement assays with an IC50 of 83nM for ALK1 and 13 nM for ALK2.M4K2234 exhibits only very weak potency against ALK4/5.M4K2234 affects phosphorylation of SMAD1/5/8 that corresponds to BMP branch of signalling which is mediated, besides others, also by ALK1/2 kinases.M4K2234 has only a very weak effect on SMAD2/3 phosphorylation that corresponds to TGF beta branch of signalling which is mediated mostly via ALK4/5/7.

M4076 is a higly potent, selective, ATP-competitive inhibitor of ATM kinase with IC50 of 0.2 nM.M4076 sensitizes tumor cell lines to radiation therapy in vitro and strongly enhances the anti-tumor activity of ionizing radiation in vivo.

LY2775240 (LY-2775240) is a highly selective, potent and orally active inhibitor of phosphodiesterase 4 (PDE4) with IC50 of 0.09/0.09/2.4/0.14 nM for PDE4A/B/C/D.LY2775240 displays >200-fold selectivity over PDE10A, and >5000-fold selectivity over other PDE isoforms (IC50>10 uM).LY2775240 potently inhibits TNFα secreted induced by Toll‐like receptor 4 agonist LPS in a human whole blood assay, inhibited LPS‐stimulated TNFα but has no effect with the media‐only control.LY2775240 is more potent than apremilast (IC50, 18 nM vs. 290 nM), also affects E‐selectin, secreted IgG, plasminogen activator inhibitor‐1, and secreted IL‐10.

LSN3172176 is a novel potent, selectiive M1 mAChR partial agonist (EC50 2.4-7.0nM, Emax 43%-73%), shows binding selectivity for M1 mAChRs (Kd=1.5 nM); LSN3172176 is a potential PET tracer for assessment of M1 mAChR target engagement in the clinic and to further elucidate the function of M1 mAChRs in health and disease.

LSH-A54 is a potent, class I selective HDAC inhibitor with IC50 of 26.2 nM (HDAC1) and 59.3 nM (HDAC2); LSH-A54 displays no significant inhibition against HADC3/6 (IC50>10 uM). LSH-A54 exhibits antiproliferative properties against breast cancer cell lines T-47D (IC50=1.58 uM), MCF-7 (IC50=1.32 uM) and BT-474 (IC50=2.55 uM). LSH-A54 attenuates cell migration significantly in wound healing assay and comparably to the pan-HDACi vorinostat, whereas the HDAC1-3 selective HDACi entinostat has no significant effect on cell migration. LSH-A54 reduced the number of colonies significantly in clonogenic survival assay compared to entinostat and showed comparable activity to pan-HDACi vorinostat.

LS-106 is a novel, fourth‐generation EGFR inhibitor against C797S mutation, targeting both EGFR19del/T790M/C797S and EGFRL858/T790M/C797S with selectivity over EGFRwt.LS-106 potently and dose‐dependently inhibited the kinase activity of EGFR19del/T790M/C797S, EGFRL858R/T790M/C797S, EGFRL858R/T790M, and EGFR19del/T790M with IC50 values of 2.4 nM, 3.1 nM, 7.3 nM, and 74.1 nM, respectively.LS-106 exhibited much weaker effect against EGFRwt (IC50=151.5 nM) and EGFR19del (IC50=402.9 nM).LS‐106 not only strongly inhibited the EGFR‐C797S-mutant kinase but also inhibited some other kinases, such as RET, ACK1, and PDGFR‐β.LS‐106 not only inhibited the proliferation of BaF3‐EGFR19del/T790M cells (IC50= 0.09 uM) but also showed over 30‐fold stronger antigrowth activity than osimertinib in BaF3‐EGFR19del/T790M/C797S (IC50= 0.09 uM) and BaF3‐EGFRL858R/T790M/C797S (IC50= 0.12 uM) cells, respectively, elicits significant cell apoptosis in EGFR–triple‐mutant cells.Oral administration of LS‐106 (30 and 60 mg/kg) potently inhibited tumor progression in PC‐9‐OR NSCLC xenograft model with TGI of 83.5% and 136.6%, respecitvely.

LPXC-516 is a potent bacterial LpxC inhibitor with IC50 of 0.68 nM (P. aeruginosa LpxC), potent against the P. aeruginosa isolates with MIC90 of 2 ug/mL.

Lockdown is a selective, reversible and non-competitive inhibitor of the integrin phosphatase PPM1F (IC50=16.37 uM), blocks cancer cell invasion.Lockdown acts in a dose-dependent, allosteric manner with high selectivity for PPM1F.Lockdown does not inhibit other protein phosphatases (PTP1P, PTPRJ, PP5) in vitro and does not induce additional phenotypes in PPM1F knockout cells.Lockdown fully re-capitulated the phenotype of PPM1F-deficient cells, increased phosphorylation of PPM1F substrates and corruption of integrin-dependent cellular processes in Lockdown treated glioblastoma cells.Phosphatase PPM1F is a regulator of cell adhesion by fine-tuning integrin activity and actin cytoskeleton structures. Elevated expression of this enzyme in human tumors is associated with high invasiveness, enhanced metastasis, and poor prognosis.

Lockdown Ester Prodrug (Lockdown Pro) is the ester-modified Lockdown with increased membrane permeability and prodrug-like properties, a selective small-molecule inhibitor of the integrin phosphatase PPM1F, blocks cancer cell invasion.Lockdown Ester Prodrug (Lockdown Pro) effectively block PPM1F-mediated effects on integrin β1 and PAK in cells, Lockdown Pro suppresses tissue invasion by PPM1F-overexpressing human cancer cells.