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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SNX-2112(PF-04928473)

SNX-2112 is an orally active Hsp90 inhibitor, with a Kd of 16 nM for Hsp90 and IC50s of 30 nM, 30 nM for Hsp90 α and Hsp90 β, also induces Her-2 degradation, and inhibits Grp94 and Trap-1, with IC50s of 10 nM, 4.275 μM and 0.862 μM, respectively.

  • CAS Number: 908112-43-6
  • MF: C23H27F3N4O3
  • MW: 464.481
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 619.8±55.0 °C at 760 mmHg
  • Melting Point: 265-266℃
  • Flash Point: 328.6±31.5 °C

K777

K777 is a potent, orally active and irreversible cysteine protease inhibitor. K777 is also a potent CYP3A4 inhibitor with an IC50 of 60 nM and a selective CCR4 antagonist featuring the potent chemotaxis inhibition. K777 irreversibly inhibits Cruzain, the major cysteine protease of Trypansoma cruzi, and cathepsins B and L. K777 is a broad-spectrum antiviral by targeting cathepsin-mediated cell entry. K777 inhibits SARS-CoV and EBOV pseudovirus entry with IC50 values of 0.68 nM and 0.87 nM, respectively[1][2][3].

  • CAS Number: 233277-99-1
  • MF: C32H38N4O4S
  • MW: 574.73
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3',4',7,8-Tetrahydroxyflavone

7,8,3′,4′-Tetrahydroxyflavone (compound 2) is a potent xanthine oxidase (XOD) inhibitor with an IC50 value of 10.488 µM[1].

  • CAS Number: 3440-24-2
  • MF: C15H10O6
  • MW: 286.24
  • Catalog: Xanthine Oxidase
  • Density: 1.654g/cm3
  • Boiling Point: 618.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 240.6ºC

VU0364739

VU0364739 is a selective PLD2 inhibitor (IC50: 22 nM). VU0364739 decreases cancer cell proliferation[1].

  • CAS Number: 1244639-78-8
  • MF: C26H27FN4O2
  • MW: 446.52
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML 351

ML351 is a potent and highly specific 15-LOX-1 inhibitor with an IC50 of 200 nM. ML351 shows excellent selectivity (>250-fold) versus the related isozymes, 5-LOX, platelet 12-LOX, 15-LOX-2, ovine COX-1, and human COX-2[1]. ML351 prevents dysglycemia and reduces β-cell oxidative stress in nonobese diabetic mouse model of T1D[2].

  • CAS Number: 847163-28-4
  • MF: C15H11N3O
  • MW: 249.267
  • Catalog: 5-Lipoxygenase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 507.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 260.6±32.9 °C

SB-435495 ditartrate

SB-435495 ditartrate is a potent, selective, reversible, non-covalent and orally active Lp-PLA2 inhibitor with an IC50 of 0.06 nM[1][3].

  • CAS Number: 304694-43-7
  • MF: C46H52F4N6O14S
  • MW: 1021.00
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Abiraterone

Abiraterone is a potent, selective, and irreversible CYP17 inhibitor with IC50 of 2 to 4 nM.

  • CAS Number: 154229-19-3
  • MF: C24H31NO
  • MW: 349.509
  • Catalog: Cytochrome P450
  • Density: 1.14g/cm3
  • Boiling Point: 500.2±50.0 °C at 760 mmHg
  • Melting Point: 227-228 °C
  • Flash Point: 256.3±30.1 °C

MMP-2 Inhibitor I

MMP-2 Inhibitor I (OA-Hy) is a potent MMP-2 inhibitor with a Ki of 1.7 μM[1][2].

  • CAS Number: 10335-69-0
  • MF: C18H35NO2
  • MW: 297.47600
  • Catalog: MMP
  • Density: 0.921g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ARN19874

ARN19874 is a selective, reversible uncompetitive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) activity inhibitor with an IC50 of ~34 μM[1].

  • CAS Number: 2190502-57-7
  • MF: C19H14N4O4S
  • MW: 394.40
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aldehyde dehydrogenase (NAD(P))

Aldehyde dehydrogenase NAD(P) (ALDH) catalyzes the oxidation of aldehydes into their corresponding carboxylic acids with the concomitant reduction of the cofactor NAD(P) into NAD(P)H, is often used in biochemical studies. The aldehyde dehydrogenases (ALDHs) are one of many enzyme systems the body utilizes to alleviate aldehyde stress[1].

  • CAS Number: 9028-88-0
  • MF:
  • MW:
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HaloPROTAC-E

HaloPROTAC-E is a novel HaloPROTAC potent degrader, inducing reversible degradation of two endosomally localized proteins, SGK3 and VPS34, with a DC50 of 3-10 nM, remarkably selective inducing only degradation of the Halo tagged endogenous VPS34 complex (VPS34, VPS15, Beclin1, and ATG14).

  • CAS Number: 2365478-58-4
  • MF: C39H56ClN5O8S
  • MW: 790.41
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Verucopeptin

Verucopeptin is a potent HIF-1 (IC50=0.22 μM) inhibitor and decreases the expression of HIF-1 target genes and HIF-1α protein levels[1][2]. Verucopeptin strongly inhibits v-ATPase activity by directly targeting the v-ATPase ATP6V1G subunit but not ATP1V1B2 or ATP6V1D. Verucopeptin exhibits antitumor activity against multidrug resistance (MDR) cancers and can be used for cancer research[3].

  • CAS Number: 138067-14-8
  • MF: C43H73N7O13
  • MW: 896.07900
  • Catalog: Proton Pump
  • Density: 1.27g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NBD-125

NBD-125 (B-12), a berberine analogue, is an RXRα activator, with an IC50 of 31.10 μM in KM12C cell[1].

  • CAS Number: 2367641-24-3
  • MF: C19H18ClNO2
  • MW: 327.80
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Integracin B

Integracin B is a potent dimeric alkyl aromatic inhibitor of HIV-1 integrase discovered from the screening of fungal extracts using an in vitro assay. Integracin B inhibits both coupled and strand transfer activity of HIV-1 integrase[1].

  • CAS Number: 224186-05-4
  • MF: C35H54O7
  • MW: 586.79900
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AN-2728

Crisaborole (AN-2728) is a potent inhibitor of PDE4 and cytokine release; inhibit PDE4 with an IC50 of 0.49 μM.

  • CAS Number: 906673-24-3
  • MF: C14H10BNO3
  • MW: 251.045
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 425.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 211.4±31.5 °C

LONAFARNIB

(Rac)-Lonafarnib (Sch66336 racemate) is the racemate of Lonafarnib. Lonafarnib is a potent and orally active farnesyl transferase (FTase) inhibitor. Lonafarnib inhibits the activities of H-ras, K-ras and N-ras with IC50 values of 1.9 nM, 5.2 nM and 2.8 nM, respectively. Lonafarnib also has anti-hepatitis delta virus (HDV) activities[1].

  • CAS Number: 193275-86-4
  • MF: C27H31Br2ClN4O2
  • MW: 638.822
  • Catalog: Farnesyl Transferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 710.4±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 383.5±35.7 °C

Tilpisertib fosmecarbil

Tilpisertib fosmecarbil is a potent serine/threonine kinase inhibitor. Tilpisertib fosmecarbil has anti-inflammatory activity[1].

  • CAS Number: 2567459-64-5
  • MF: C35H36ClN8O7P
  • MW: 747.14
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NDI-091143

NDI-091143 is a novel ATP-citrate lyase inhibitor.

  • CAS Number: 2375840-87-0
  • MF: C20H14ClF2NO5S
  • MW: 453.84
  • Catalog: ATP Citrate Lyase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Desirudin

Desirudin (CGP 39393) is a thrombin inhibitor. Desirudin can inhibit the formation of blood clots and venous stasis thrombosis, which is used for the research of thrombocytopenia or platelet dysfunction[1][2].

  • CAS Number: 120993-53-5
  • MF: C287H440N80O110S6
  • MW:
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ganoderic acid B

Ganoderic acid B is a triterpene isolated from a mushroom Ganoderma lucidum. Ganoderic acid B inhibits the activation of Epstein-Barr virus (EBV) antigens as telomerase inhibitor. Ganoderic acid B is a moderately active inhibitor against HIV-1 protease[1][2][3].

  • CAS Number: 81907-61-1
  • MF: C30H44O7
  • MW: 516.666
  • Catalog: HIV Protease
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 689.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.4±28.0 °C

Ciluprevir

Ciluprevir(BILN 2061) is a specific and potent peptidomimetic inhibitor of the HCV NS3 protease with an IC50 of 3.0 nM.

  • CAS Number: 300832-84-2
  • MF: C40H50N6O8S
  • MW: 774.93
  • Catalog: HCV
  • Density: 1.4±0.0 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD7325

AZD7325 is a potent and orally active partial selective PAM of GABAAα2 and Aα3 receptor (Ki=0.3 and 1.3 nM, respectively), and has less antagonistic efficacy at the Aα1 and Aα5 receptor subtypes[1][4]. AZD7325 is a moderate CYP1A2 and a potent CYP3A4 inducer in vitro[2]. AZD7325 has the potential for the investigation of anxiety and dravet syndrome[3]. PAM: positive allosteric modulator.

  • CAS Number: 942437-37-8
  • MF: C19H19FN4O2
  • MW: 354.378
  • Catalog: GABA Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JZP-MA-11

JZP-MA-11 is a positron emission tomography (PET) ligand targeting the endocannabinoid α/β-hydrolase domain 6 (ABHD6) enzyme. JZP-MA-11 selectively inhibits ABHD6 with an IC50 value of 126 nM. JZP-MA-11 can cross the blood-brain barrier (BBB). [18F]JZP-MA-11 has the potential for preclinical evaluation targeting the brain ABHD6 in mice and nonhuman primate (NHP)[1].

  • CAS Number: 1672691-50-7
  • MF: C15H17FN4O2S
  • MW: 336.38
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Apigenin

Apigenin is a competitive CYP2C9 inhibitor with a Ki of 2 μM.

  • CAS Number: 520-36-5
  • MF: C15H10O5
  • MW: 270.237
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 555.5±50.0 °C at 760 mmHg
  • Melting Point: >300 °C(lit.)
  • Flash Point: 217.1±23.6 °C

Guggulsterone E&Z

Guggulsterone is a plant sterol derived from the gum resin of the tree Commiphora wightii. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases and JNK, inhibition of Akt[1]. Guggulsterone, a farnesoid X receptor (FXR) antagonist, decreases CDCA-induced FXR activation with IC50s of 17 and 15 μM for Z- and E-Guggulsterone, respectively[2].

  • CAS Number: 95975-55-6
  • MF: C21H28O2
  • MW: 312.446
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 463.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.3±25.7 °C

N[2-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]quinoline-3-carboxamide Hydrochloride

BML-280 (VU0285655-1) is a potent and selective phospholipase D2 (PLD2) inhibitor. BML-280 has the ability to prevent caspase-3 cleavage and reduction in cell viability induced by high glucose. BML-280 can be used for rheumatoid arthritis research[1][2].

  • CAS Number: 1158347-73-9
  • MF: C25H27N5O2
  • MW: 429.51400
  • Catalog: Interleukin Related
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MLN-4760

MLN-4760 is a potent and selective human ACE2 inhibitor (IC50, 0.44 nM), with excellent selectivity (>5000-fold) versus related enzymes including human testicular ACE (IC50, >100 μM) and bovine carboxypeptidase A (CPDA; IC50, 27 μM).

  • CAS Number: 305335-31-3
  • MF: C19H23Cl2N3O4
  • MW: 428.31000
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kushenol B

Kushenol B is an isoprenoid flavonoid isolated from S. flavescens, has antimicrobial, anti-inflammatory and antioxidant activities[1]. Kushenol B has inhibitory activity against cAMP phosphodiesterase (PDE), with an IC50 of 31 µM[1].

  • CAS Number: 99217-64-8
  • MF: C30H36O6
  • MW: 492.603
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 702.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 228.2±26.4 °C

ER-000444793

ER-000444793 is a potent inhibitor of mitochondrial permeability transition pore (mPTP) opening. ER-000444793 inhibits mPTP with an IC50 of 2.8 μM.

  • CAS Number: 792957-74-5
  • MF: C23H18N2O2
  • MW: 354.4
  • Catalog: Mitochondrial Metabolism
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M5N36

M5N36 is a potent and selective Cdc25C inhibitor with IC50 values of 0.15, 0.19, 0.06 µM for Cdc25A, Cdc25B, Cdc25C, respectively. M5N36 shows anti-proliferative activity and increases the expression of p-CDK1 and p-CDK2[1].

  • CAS Number: 2832887-40-6
  • MF: C20H16ClN5O3
  • MW: 409.83
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A