acs

IACS-52825 is a selective and potent dual leucine zipper kinase (DLK) inhibitor that reverses para-mechanical aberrant pain in a CIPN mouse model for the study of neurological disorders.

IACS-010759 is an orally bioavailable inhibitor of complex I of oxidative phosphorylation of the mitochondrial electron transport chain.

Megestrol acetate (BDH1298) is a progestogen with actions and uses similar to those of the progestogens in general. Megestrol acetate also has anti-androgenic properties. It is given by mouth in the palliative treatment or as an adjunct to other therapy in endometrial carcinoma and in breast cancer. Megestrol acetate has been approved to treat anorexia and cachexia.

IACS-13909 (BBP-398), a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway.

Ticagrelor metabolite M5 (T437700) is a metabolite of Ticagrelor, the first reversible oral antagonist of P2Y12 receptor. Compared to Clopidogrel, Ticagrelor has faster and more consistent inhibition on ADP-receptors. Ticagrelor is used in the treatment of acute coronary syndromes (ACS).

Iodofiltic acid can be used in the adjuvant treatment of acute coronary syndromes (Zeus ACS) and can be imaged to detect myocardial ischemia.

IACS-8803 is a potent cyclic dinucleotide STING agonist that exhibits strong systemic antitumor efficacy.

IACS-8779 is a potent STING agonist that efficiently stimulates interferon gene activity and exhibits strong systemic antitumor effects.

IACS-8968 R-enantiomer is the R-enantiomer of IACS-8968. IACS-8968 is a dual IDO and TDO inhibitor (pIC50s: 6.43 for IDO and <5 for TDO).

PHD2 HDACs-IN-1 is a potent mixed inhibitor of PHD2 HDACs, acting on PHD2 (IC50: 1.15 μM), HDAC1 (IC50: 19.75 μM), HDAC2 (IC50: 26.60 μM), and HDAC16 (IC50: 15.98 μM). HDACs-IN-1 is a low toxicity nephroprotective agent suitable for studies of cisplatin-induced acute kidney injury (AKI).

IACS-15414 is a potent SHP2 inhibitor that is effective when administered orally, demonstrating an IC50 value of 122 nM.

Triacsin C (WS 1228A) from Streptomyces aureofaciens is a differential inhibitor of arachidonic acid coenzyme A synthetase and non-specific long-chain acyl-coenzyme A synthetase, with anti-atherosclerotic activity, inhibition of ACSL activity, and inhibition of the accumulation of TAGs into lipid droplets (LDs).Triacsin C has been used to study rotavirus infection and Alzheimer;s disease. Triacsin C is used to study rotavirus infection and Alzheimer;s disease.

IACS-9439 is a potent, selective, and orally active CSF1R inhibitor with a K(i) of 1 nM, suitable for research on advanced solid tumors [1].

IACS-9571 (ASIS-P040) hydrochloride is a potent, selective inhibitor of TRIM24 and BRPF1, with an IC50 of 8 nM for TRIM24, and dissociation constants (Kd) of 31 nM for TRIM24 and 14 nM for BRPF1.

ACSS2-IN-1 is a potent ACSS2 inhibitor with IC50 values ranging from 0.01 nM to <1 nM, suitable for cancer research.

GlcNAcstatin, a selective glucoimidazole-based inhibitor of bacterial O-GlcNAcase, exhibits a K_i value of 4.6 pM and demonstrates a specificity that is 100,000-fold greater than that for HexA/B [1].

IACS-8803 Disodium, a potent cyclic dinucleotide STING agonist, exhibits strong systemic antitumor efficacy [1].

IACS-8803 diammonium, a potent cyclic dinucleotide STING agonist, demonstrates robust systemic antitumor efficacy [1].

IACS-4759 is a novel potent and selective MTH1 inhibitor with excellent cell permeability and good metabolic stability in microsomes.

IACS-010759 is a potent inhibitor of complex I of OXPHOS with orally bioavailable. IACS-10759 effectively inhibits ATP production and oxygen consumption in isolated mitochondria, and inhibits the conversion of NADH to NAD+ in immunoprecipitated complex I

ACSS2-IN-2 (MTB-9655) is an inhibitor of acyl-CoA synthetase short-chain family member 2 (ACSS2). ACSS2-IN-2 can inhibit ACSS2 activity with an IC50 value of 3.8 nM. ACSS2-IN-2 can be used for the research of several diseases, such as viral infection, metabolic disorders, neuropsychiatric diseases, inflammatory autoimmune conditions and cancer.

GW5638 is a estrogen receptor ligand. GW5638 is a prodrug of its active metabolite GW7604. GW5638 appears to act as an antagonist in these in vitro systems, although in a manner distinct from other known ER modulators. GW5638 is also classified as a pseud

ACSF is often used as a replacement of CSF for perfusion of brain slices to preserve interneurons. ACSF is invented to reduce the incidence of cerebral edema and further suppress brain cell disorders. And ACSF is often used as an irrigation fluid or perfu

IACS-9571 is a selective and potent inhibitor of TRIM24 and BRPF1, (IC50: 8 nM for TRIM24; Kds: 31 nM and 14 nM for TRIM24 and BRPF1).

IACS-8779 disodium, a highly potent STING (stimulator of interferon genes) agonist, demonstrates robust activation of the STING pathway in vitro, along with superior systemic antitumor efficacy. This compound shows a significant anti-tumor response in the B16 murine melanoma model, indicating its potential for effective cancer therapy.

IACS-8968 S-enantiomer is the S-enantiomer of IACS-8968. IACS-8968 is a dual IDO and TDO inhibitor (pIC50s: 6.43 for IDO and <5 for TDO).

IACS-8968 is a dual IDO and TDO inhibitor (pIC50s: 6.43 for IDO and <5 for TDO).

HDACs mTOR Inhibitor 1 is a dual HDAC and mammalian target of Rapamycin (mTOR) inhibitor for treating hematologic malignancies, with IC50 values of 0.19 nM, 1.8 nM, 1.2 nM, and >500 nM for HDAC1, HDAC6, mTOR, and PI3Kα, respectively.

Desmethylanethol trithione (ADT-OH) is a derivative of anethole dithiolethione (ADT) and synthetic hydrogen sulfide (H2S) donor. In the in vitro glucose-oxygen deprivation (OGD) model, Desmethylanethol trithione markedly attenuated tPA-enhanced Akt activation and VEGF expression in brain microvascular endothelial cells. Finally, Desmethylanethol trithione improved functional outcomes in mice subjected to MCAO and tPA infusion. H2S donors reduced tPA-induced cerebral hemorrhage by possibly inhibiting the Akt-VEGF-MMP9 cascade. Administration of H2S donors has potential as a novel modality to improve the safety of tPA following the stroke.

Photoswitchable PAD inhibitor is a photoactivated protein arginine deiminase (PAD) inhibitor and a derivative of BB-Cl-amidine that contains an azobenzene photoswitch allowing optical control of PAD activity.1 Without photoactivation, it is a weak inhibitor of PAD2 (IC50 = >100 μM) and is less potent than BB-Cl-amidine in inhibiting citrulline production in vitro (kinact/KIs = 2,300, 600, 1,000, and 10,510 M-1min-1 for PAD1-4, respectively) and does not inhibit histone H3 citrullination in HEK293T cells overexpressing PAD2 when used at concentrations up to 100 μM. However, it can rapidly be photoactivated with UV-A radiation to the more active cis-isomer, which is an irreversible, competitive inhibitor of histone H3 citrullination with an IC50 value of 9.1 μM.References1. Mondal, S., Parelkar, S.S., Nagar, M., et al. Photochemical control of protein arginine deiminase (PAD) activity. ACS Chem. Biol. 13(4), 1057-1065 (2018). Photoswitchable PAD inhibitor is a photoactivated protein arginine deiminase (PAD) inhibitor and a derivative of BB-Cl-amidine that contains an azobenzene photoswitch allowing optical control of PAD activity.1 Without photoactivation, it is a weak inhibitor of PAD2 (IC50 = >100 μM) and is less potent than BB-Cl-amidine in inhibiting citrulline production in vitro (kinact/KIs = 2,300, 600, 1,000, and 10,510 M-1min-1 for PAD1-4, respectively) and does not inhibit histone H3 citrullination in HEK293T cells overexpressing PAD2 when used at concentrations up to 100 μM. However, it can rapidly be photoactivated with UV-A radiation to the more active cis-isomer, which is an irreversible, competitive inhibitor of histone H3 citrullination with an IC50 value of 9.1 μM. References1. Mondal, S., Parelkar, S.S., Nagar, M., et al. Photochemical control of protein arginine deiminase (PAD) activity. ACS Chem. Biol. 13(4), 1057-1065 (2018).

PW0464, a nanomolar potent complete G protein-biased ligand, is a noncatechol D1R agonist with an EC50 of 5.8 nM (Gs-cAMP)[1].

(S)-PI3Kα-IN-4, a potent inhibitor of PI3Kα with an IC50 of 2.3 nM, demonstrates 38.3-, 4.25-, and 4.93-fold selectivity over PI3Kβ, PI3Kδ, and PI3Kγ, respectively, and is suitable for cancer research[1]. (S)-PI3Kα-IN-4 (compound 11) is a quinazolin-4(3H)-one derivative with 2-substituted-N-methylpropanamide substitution[1].

JC-171, a selective inhibitor of the NLRP3 inflammasome, effectively inhibits LPS ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages with an IC50 of 8.45 μM[1].

Rubrofusarin triglucoside, a glycoside isolated from Cassia obtusifolia Linn seeds, demonstrates inhibitory activity against human monoamine oxidase A (hMAO-A), exhibiting an IC50 value of 85.5 μM[1].

Potent Smo antagonist (IC50 = 5 nM). Attenuates the leukemia-initiation potential of AML cells in a serial transplantation mouse model. Also eliminates self-propagation capacity of AML cells. Munchhof et al (2011) Discovery of PF-04449913, a potent and orally bioavailable inhibitor of smoothened. ACS Med.Chem.Lett. 3 106 PMID:24900436 |Fukushima et al (2016) Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells. Cancer Sci. 107 1422 PMID:27461445 |Giordani et al (2016) The human Smoothened inhibitor PF-04449913 induces exit from quiescence and loss of multipotent Drosophila hematopoietic progenitor cells. Oncotarget 7 55313 PMID:27486815

MAP4K4 (HGK) inhibitor (IC50 = 140 nM). Also inhibits MINK and TNIK (IC50 values are 8 and 13 nM, respectively). Improves fasting hyperglycemia in mice. Orally active. Ammirati et al (2015) Discovery of an in vivo tool to establish proof-of-concept for MAP4K4-based antidiabetic treatment. ACS Med.Chem.Lett. 6 1128 PMID:26617966

Selective medium-chain free fatty acid receptor GPR84 agonist (EC50 = 139 nM). Exhibits no response at GPR40, GPR41, GPR119 or GPR120 at 100 μM. Activates calcium mobilization, inhibits cAMP accumulation, and induces ERK1/2 phosphorylation, receptor desensitization and internalization in vitro. Liu et al (2016) Design and synthesis of 2-alkylpyrimidine-4,6-diol and 6-alkylpyridine-2,4-diol as potent GPR84 agonists. ACS Med.Chem.Lett. 7 579 PMID:27326330 |Zhang et al (2016) Discovery and characterization of a novel small-molecule agonist for medium-chain free fatty acid receptor G protein-coupled receptor 84. J.Pharmacol.Exp.Ther. 357 337 PMID:26962172

SR 1903 is a modulator of retinoic acid receptor-related orphan receptor γ (RORγ) and liver X receptor (LXR).1 It is an inverse agonist of RORγ (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor γ (PPARγ; IC50 = 209 nM) but does not activate it. SR 1903 (10 μM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg/kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity.References1. Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019). SR 1903 is a modulator of retinoic acid receptor-related orphan receptor γ (RORγ) and liver X receptor (LXR).1 It is an inverse agonist of RORγ (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor γ (PPARγ; IC50 = 209 nM) but does not activate it. SR 1903 (10 μM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg/kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity. References1. Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019).

Rab8a GTPase-binding stapled peptide (Kd = 12.7 μM). Cell permeable; localizes to the endomembrane system. Cromm et al (2016) Protease-resistant and cell-permeable double-stapled peptides targeting the Rab8a GTPase. ACS Chem.Biol. 11 2375 PMID:27336832

PI3Kα-IN-4 is a potent, selective, and orally active PI3Kα inhibitor with an IC50 of 1.8 nM, demonstrating antitumor activity [1].

TAK1-IN-2 is a potent and selective TAK1 inhibitor with an IC50 of greater than 2 nM [1].

Acyl coenzyme A synthetase (ACS), also known as acetyl coenzyme A synthetase, catalyzes the activation of fatty acids via coenzyme A through a two-step thioesterification process, forming acyl coenzyme A. It is crucial in anabolic and catabolic lipid metabolism pathways and contributes to the tricarboxylic acid (TCA) cycle during aerobic respiration [1].