Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. In each pathway, enzymes catalyze the conversion of substrates into structurally similar products. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Metabolism maintains the living state of the cells and the organism.

Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. Proteases can not only activate proteins such as cytokines, or inactivate them such as numerous repair proteins during apoptosis, but also expose cryptic sites, such as occurs with β-secretase during amyloid precursor protein processing, shed various transmembrane proteins such as occurs with metalloproteases and cysteine proteases, or convert receptor agonists into antagonists and vice versa such as chemokine conversions carried out by metalloproteases, dipeptidyl peptidase IV and some cathepsins. In addition to the catalytic domains, a great number of proteases contain numerous additional domains or modules that substantially increase the complexity of their functions.

Imbalances in metabolic activities have been found to be critical in a number of pathologies, such as cardiovascular diseases, inflammation, cancer, and neurodegenerative diseases.

References:
[1] Turk B, et al. EMBO J. 2012 Apr 4;31(7):1630-43.
[2] Eatemadi A, et al. Biomed Pharmacother. 2017 Feb;86:221-231.


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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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Cabotegravir

Cabotegravir is a potent HIV integrase inhibitor as an oral lead-in tablet and long-acting injectable for the treatment and prevention of HIV infection. Cabotegravir is an inhibitor of OAT1 (IC50 0.81 μM) and OAT3 (IC50 0.41 μM).IC50 value: 0.81 μM (OAT1), 0.41 μM (OAT3) [1]Target: OAT1, OAT3Cabotegravir is a potent HIV integrase inhibitor in clinical development as an oral lead-in tablet and long-acting injectable for the treatment and prevention of HIV infection.[2] Cabotegravir is an HIV-1 integrase inhibitor under development as a tablet for both oral lead-in therapy and long-acting (LA) injectable for intramuscular dosing.[3]

  • CAS Number: 1051375-10-0
  • MF: C19H17F2N3O5
  • MW: 405.352
  • Catalog: HIV
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 664.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.4±31.5 °C

H-Glu-Ala-Gly-Asp-Asp-Ile-Val-Pro-Cys-Ser-Met-Ser-Tyr-Thr-Trp-Thr-Gly-Ala-OH

Hepatitis C Virus S5A/5B is a synthetic peptide substrate. Hepatitis C Virus S5A/5B mimics the NS5A/5B junction of the nonstructural protein (NS), served as the substrate for the study of HCV NS3 protease activity[1].

  • CAS Number: 191529-67-6
  • MF: C81H119N19O30S2
  • MW: 1903.051
  • Catalog: HCV Protease
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 2224.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1299.1±34.3 °C

Fosamprenavir (Calcium Salt)

GW433908 is a phosphate ester prodrug of the antiretroviral protease inhibitor amprenavir, with improved solubility over the parent molecule and a potential for reduced pill burden on current dosing regimens; GW433908G is the calcium salt of the prodrug.IC50 Value:Target: HIV Proteasein vitro: There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine[1].in vivo: Fosamprenavir-ritonavir administered with methadone did not alter plasma amprenavir pharmacokinetics compared with historical control data; nor did it alter the unbound R-methadone at 2 and 6 hours after methadone dosing. Pharmacodynamic indexes remained essentially unchanged after adding fosamprenavir-ritonavir to methadone [2]. After a high-fat meal compared with fasting, (1) the bioavailability of GW433908G suspension was decreased by 20% and Cmax by 41%, and (2) for GW433908G tablets, there was no influence on AUC(12% lower Cmax). After a low-fat meal compared with fasting, (1) there was bioequivalence for GW433908G tablets, but (2) bioavailability was decreased by 23% for amprenavir capsules (Cmax was also lower, by 46%) [3].Clinical trial: Study of an Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects. Phase 2

  • CAS Number: 226700-81-8
  • MF: C25H34CaN3O9PS
  • MW: 623.669
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 282-284ºC
  • Flash Point: N/A

Prunetin

Prunetin, an O-methylated isoflavone, possesses anti-inflammatory activity. Prunetin is a potent human aldehyde dehydrogenases inhibitor[1][2].

  • CAS Number: 552-59-0
  • MF: C16H12O5
  • MW: 284.263
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 546.5±50.0 °C at 760 mmHg
  • Melting Point: 240-242ºC
  • Flash Point: 209.7±23.6 °C

RORγt Inverse agonist 10

RORγt Inverse agonist 10 is a potent and orally bioavailable RORγt (retinoic acid receptor-related orphan nuclear receptor gamma t) inverse agonist, with an IC50 of 51 nM. RORγt is a major transcription factor of genes related to psoriasis pathogenesis such as IL-17A, IL-22, and IL-23R[1]

  • CAS Number: 2413986-35-1
  • MF: C25H26F6N6O3
  • MW: 572.50
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AHU-377 hemicalcium salt

Sacubitril (AHU-377) hemicalcium salt is a potent NEP inhibitor with an IC50 of 5 nM. Sacubitril hemicalcium salt is a component of the heart failure medicine LCZ696.

  • CAS Number: 1369773-39-6
  • MF: C24H28Ca0.5NO5
  • MW: 430.52
  • Catalog: Neprilysin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SR 0987

SR0987 is a RORγt agonist, with an EC50 of 800 nM.

  • CAS Number: 303126-97-8
  • MF: C16H10ClF6NO2
  • MW: 397.699
  • Catalog: ROR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 378.8±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 182.9±27.9 °C

Metolazone-d7

Metolazone-d7 is deuterium labeled Metolazone. Metolazone (SR-720-22) is primarily used to treat congestive heart failure and high blood pressure.

  • CAS Number: 2714484-71-4
  • MF: C16H9D7ClN3O3S
  • MW: 372.88
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M77976

M77976 is a specific ATP-competitive inhibitor of PDK4 (pyruvate dehydrogenase kinase isoforms 4), with an IC50 of 648 μM. M77976 is potential for the research of obesity and diabetes[1].

  • CAS Number: 394237-61-7
  • MF: C17H16N2O3
  • MW: 296.32
  • Catalog: PDHK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Atazanavir-d6

Atazanavir-d6 is deuterium labeled Atazanavir. Atazanavir (BMS-232632), a highly selective HIV-1 protease inhibitor, is the first protease inhibitor approved for once-daily administration[1]. Atazanavir (BMS-232632) is a substrate and inhibitor of CYP3A4, and an inhibitor and inducer of P-glycoprotein (P-gp)[2]. Atazanavir is also a SARS-CoV 3CLpro inhibitor with an IC50 of 3.49 μM[3].

  • CAS Number: 1092540-50-5
  • MF: C38H46D6N6O7
  • MW: 710.89
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 200-205°C
  • Flash Point: N/A

CDC801

CDC801 is a potent and orally active phosphodiesterase 4 (PDE4) and tumor necrosis factor-α (TNF-α) inhibitor with IC50 of 1.1 μM and 2.5 μM, respectively.

  • CAS Number: 192819-27-5
  • MF: C23H24N2O5
  • MW: 408.45
  • Catalog: TNF Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPP1-IN-1 hydrate

DPP1-IN-1 hydrate is a DPP1 inhibitor (IC50: 1.6 nM). DPP1-IN-1 hydrate has good bioavailability and pharmacokinetic characteristics, and can be used for research of inflammatory disease[1].

  • CAS Number: 2971064-13-6
  • MF: C23H25FN4O5
  • MW: 456.47
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FAAH-IN-1

FAAH-IN-1 is a fatty acid amide hydrolase (FAAH) inhibitor, with IC50s of 145 nM and 650 nM for rat and human FAAH, respectively.

  • CAS Number: 1242441-47-9
  • MF: C20H19ClN4OS
  • MW: 398.91
  • Catalog: FAAH
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Leelamine hydrochloride

Leelamine hydrochloride is a tricyclic diterpene molecule that is extracted from the bark of pine trees[1]. Leelamine hydrochloride is a cannabinoid receptor type 1 (CB1) agonist and a inhibitor of SREBP1-regulated fatty acid/lipid synthesis in prostate cancer cells that is not affected by androgen receptor status. Leelamine hydrochloride suppresses transcriptional activity of androgen receptor, which is known to regulate fatty acid synthesis[2,3].

  • CAS Number: 16496-99-4
  • MF: C20H32ClN
  • MW: 321.928
  • Catalog: Cannabinoid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sivelestat Sodium

Sivelestat sodium(ONO5046; LY544349; EI546) is a competitive inhibitor of human neutrophil elastase(IC50 = 44 nM; Ki=200 nM); also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse.IC50 value: 44 nM [1]Target: neutrophil elastaseONO-5046 did not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 microM. In in vivo studies, ONO-5046 suppressed lung hemorrhage in hamster (ID50 = 82 micrograms/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID50 = 9.6 mg/kg) by intravenous administration, both of which were induced by human neutrophil elastase [1]. Sivelestat sodium hydrate is an anti-neutrophil elastase inhibitor and may be one of the treatment options for acute respiratory failure due to pneumocystis pneumonia in AIDS patients [2].

  • CAS Number: 150374-95-1
  • MF: C20H21N2NaO7S
  • MW: 456.445
  • Catalog: Elastase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

17-AEP-GA

17-AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion. ADCs Toxin[1].

  • CAS Number: 75747-23-8
  • MF: C34H50N4O8
  • MW: 642.78
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RS6212

RS6212 is a specific LDH (lactate dehydrogenase) inhibitor with an IC50 value of 12.03 μM . RS6212 inhibits tumor growth and exhibits potent anticancer activity in multiple cancer cell lines[1].

  • CAS Number: 2097925-52-3
  • MF: C20H22N4O3S
  • MW: 398.48
  • Catalog: Lactate Dehydrogenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Autotaxin-IN-4

Autotaxin-IN-4 (compound 51), extracted from patent WO2018212534A1, is an Autotaxin inhibitor. Autotaxin-IN-4 has the potential to treat idiopathic pulmonary fibrosis[1].

  • CAS Number: 2156655-86-4
  • MF: C22H21N9O2
  • MW: 443.46
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis(maltolato)oxovanadium(IV)

Bis(maltolato)oxovanadium(IV) (BMOV) is a potent, reversible, competitive and orally active pan-PTP (protein tyrosine phosphatases) inhibitor. Bis(maltolato)oxovanadium(IV) inhibits HCPTPA, PTP1B, HPTPβ and SHP2 with IC50s of 126 nM, 109 nM, 26 nM and 201 nM, respectively. Bis(maltolato)oxovanadium(IV) is a potent insulin sensitizer[1][2].

  • CAS Number: 38213-69-3
  • MF: C12H10O7V
  • MW: 317.145
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: 284.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 127.3ºC

XL335

WAY-362450 is a potent, selective, and orally bioavailable FXR agonist with EC50 of 4 nM.

  • CAS Number: 629664-81-9
  • MF: C25H24F2N2O3
  • MW: 438.466
  • Catalog: FXR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 617.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 327.1±31.5 °C

BMS-852927

BMS-852927 is an LXRβ-selective agonist.

  • CAS Number: 1256918-39-4
  • MF: C29H28Cl2F2N2O4S
  • MW: 609.51
  • Catalog: LXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L791943

L791943 is a potent, selective Phosphodiesterase-4 (PDE4) inhibitor with an IC50 of 4.2 nM.

  • CAS Number: 192767-01-4
  • MF: C24H17F10NO4
  • MW: 573.38
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Glucosamine-15N hydrochloride

Glucosamine-15N hydrochloride is the 15N labeled Glucosamine hydrochloride. Glucosamine hydrochloride (D-Glucosamine hydrochloride) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids, is used as a

  • CAS Number: 42927-60-6
  • MF: C6H14ClNO5
  • MW: 216.62500
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Autotaxin-IN-5

Autotaxin-IN-5 (compound 63), extracted from patent WO2018212534A1, is an Autotaxin inhibitor. Autotaxin-IN-5 has the potential to treat idiopathic pulmonary fibrosis[1].

  • CAS Number: 2156655-99-9
  • MF: C30H29N9O2
  • MW: 547.61
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMP-PCP

AMP-PCP is an ATP analogue and can bind to Hsp90 N-terminal domain with a Kd value of 3.8 μM. AMP-PCP binding favors the formation of the active homodimer of Hsp90[1].

  • CAS Number: 3469-78-1
  • MF: C11H18N5O12P3
  • MW: 505.20800
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oxylone acetate

Fluorometholone acetate is a synthetic glucocorticoid corticosteroid and a corticosteroid ester. Fluorometholone acetate potently inhibits carbonic anhydrase (CA) with IC50s of 2.18 μM and 17.5 μM for hCA-I and hCA-II, respectively. Fluorometholone acetate has anti-inflammatory effect and has the potential for external ocular inflammation research[1][2][3].

  • CAS Number: 3801-06-7
  • MF: C24H31FO5
  • MW: 418.498
  • Catalog: Carbonic Anhydrase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 532.1±50.0 °C at 760 mmHg
  • Melting Point: 230-232°
  • Flash Point: 275.6±30.1 °C

Teneligliptin D8

Teneligliptin D8 (MP-513 D8) a deuterium labeled Teneligliptin (MP-513). Teneligliptin is a potent, orally available, competitive, and long-lasting DPP-4 inhibitor[1].

  • CAS Number: 1391012-95-5
  • MF: C22H22D8N6OS
  • MW: 434.628
  • Catalog: Dipeptidyl Peptidase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 663.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.0±31.5 °C

SGK1-IN-4

SGK1-IN-4 (compound 17a) is a highly selective, orally active SGK1 inhibitor. SGK1-IN-4 can be used for osteoarthritis research[1].

  • CAS Number: 1628048-93-0
  • MF: C23H21ClFN5O4S
  • MW: 517.96
  • Catalog: SGK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPP1-IN-1

DPP1-IN-1 (compound 1) is a potent inhibitor of DPP1. DPP1-IN-1 can used in study bronchiectasis[1].

  • CAS Number: 2762114-61-2
  • MF: C23H23FN4O4
  • MW: 438.45
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Acetoxy-4-methylcoumarin

7-Acetoxy-4-methylcoumarin is an inhibitor of GST.7-Acetoxy-4-methylcoumarin inhibits AFB1-DNA binding in vitro with 36.7% inhibition[1][2].

  • CAS Number: 2747-05-9
  • MF: C12H10O4
  • MW: 218.20500
  • Catalog: Gutathione S-transferase
  • Density: 1.263g/cm3
  • Boiling Point: 371.4ºC at 760mmHg
  • Melting Point: 149-150 °C(lit.)
  • Flash Point: 191.5ºC