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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BMS 453

BMS453 (BMS-189453), a synthetic retinoid, is a RARβ agonist and a RARα/RARγ antagonist. BMS453 inhibits breast cell growth predominantly through the induction of active TGFβ[1][2].

  • CAS Number: 166977-43-1
  • MF: C27H24O2
  • MW: 380.47800
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(10β)-10,18-Epoxyros-15-ene-7,18-dione

Rosenonolactone shows inhibitory activity against prolyl endopeptidase and thrombin and cholesterol ester transfer protein[1][2][3].

  • CAS Number: 508-71-4
  • MF: C20H28O3
  • MW: 316.43
  • Catalog: CETP
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 449.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 196.2±28.8 °C

5-O-Feruloylquinic acid

5-Feruloylquinic acid (5-FQA) possesses antioxidative effects and tyrosinase inhibitory activities[1].

  • CAS Number: 40242-06-6
  • MF: C17H20O9
  • MW: 368.33500
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lactacystin

Lactacystin, an antibiotic Streptomyces spp. metabolite, is a potent and selective proteasome inhibitor with an IC50 of 4.8 μM for 20S proteasome. Lactacystin also inhibits the lysosomal enzyme cathepsin A[1]. Lactacystin inhibits cell growth and induces neurite outgrowth[2].

  • CAS Number: 133343-34-7
  • MF: C15H24N2O7S
  • MW: 376.425
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 714.9±60.0 °C at 760 mmHg
  • Melting Point: 233-235ºC dec.
  • Flash Point: 386.1±32.9 °C

PHPS1

PHPS1 is a potent and selective Shp2 inhibitor with Kis of 0.73, 5.8, 10.7, 5.8, and 0.47 μM for Shp2, Shp2-R362K, Shp1, PTP1B, and PTP1B-Q, respectively[1].

  • CAS Number: 314291-83-3
  • MF: C23H19N5O6S
  • MW: 493.49200
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hesperetin 7-O-glucoside

Hesperetin 7-O-glucoside is produced by the enzymatic conversion of Hesperidin. Hesperetin 7-O-glucoside is a potent human HMG-CoA reductase inhibitor and also effectively inhibits the growth of Helicobacter pylori. Antihypertensive effect[1][2].

  • CAS Number: 31712-49-9
  • MF: C22H24O11
  • MW: 464.419
  • Catalog: Bacterial
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 807.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 282.0±27.8 °C

Licofelone

Licofelone (ML-3000) is a dual COX/5-lipoxygenase (5-LOX) inhibitor for the treatment of osteoarthritis. Licofelone (ML-3000) exerts anti-inflammatory and anti-proliferative effects. Licofelone (ML-3000) induces apoptosis, and decreases the production of proinflammatory leukotrienes and prostaglandins[1][2].

  • CAS Number: 156897-06-2
  • MF: C23H22ClNO2
  • MW: 379.879
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 539.7±50.0 °C at 760 mmHg
  • Melting Point: 162-163ºC
  • Flash Point: 280.2±30.1 °C

Cryptosporioptide A

Cryptosporioptide A (Compound 3) is a pigment protein tyrosine phosphatase inhibitor derived from the insect-parasitic fungus Cordyceps gracilioides. Cryptosporioptide A inhibits PTP1B, SHP2, CDC25B, LAR and SHP1 enzymes with IC50 of 7.3, 5.7, 7.6, >50, 4.9 μg/mL, respectively[1].

  • CAS Number: 1647101-05-0
  • MF: C18H17NO10
  • MW: 407.33
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Ethoxyresorufin

7-Ethoxyresorufin (Resorufin ethyl ether) is a fluorometric substrate for and competitive inhibitor of cytochrome P450, especially CYP1A1. 7-Ethoxyresorufin also inhibits NO synthase[1][2].

  • CAS Number: 5725-91-7
  • MF: C14H11NO3
  • MW: 241.242
  • Catalog: NO Synthase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 389.3±42.0 °C at 760 mmHg
  • Melting Point: 223-225ºC(lit.)
  • Flash Point: 185.9±22.3 °C

Nampt-IN-10 TFA

Nampt-IN-10 TFA (compound 4) is a Nicotinamide Phosphoribosyltransferase (NAMPT) inhibitor. Nampt-IN-10 TFA shows cellular potency to A2780 and CORL23 cells lines with IC50s of 5 and 19 nM, respectively. Nampt-IN-10 TFA can be used as a novel non-antimitotic payload for ADCs[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Danoprevir (ITMN-191)

Danoprevir is a NS3/4A protease inhibitor for hepatitis C virus (HCV) with IC50 of 0.2-3.5 nM. The inhibition effect on HCV genotypes 1A/1B/4/5/6 is approximately 10-fold higher than 2B/3A.

  • CAS Number: 850876-88-9
  • MF: C35H46FN5O9S
  • MW: 731.831
  • Catalog: HCV
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PCSK9-IN-1

PCSK9-IN-1 is a novel and highly potent cyclic peptide PCSK9 inhibitor with a Ki value of 1.46 nM.

  • CAS Number: 2730022-10-1
  • MF: C65H80FN11O12S2
  • MW: 1290.53
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4'-Methoxyisoagarotetrol

4'-Methoxyisoagarotetrol is chromone derivative and shows moderate PDE?3A inhibitory activity (IC50=54 μM)[1].

  • CAS Number: 104901-10-2
  • MF: C18H20O7
  • MW: 348.35
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PCSK9-IN-16

PCSK9-IN-16 is a potent PCSK9 inhibitor. PCSK9-IN-16 is extracted from patent WO2020150474, example 87, has the potential for hypercholesterolemia and other cardiovascular diseases research[1].

  • CAS Number: 2455424-51-6
  • MF: C16H20N6O2S3
  • MW: 424.56
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Autotaxin-IN-3

Autotaxin-IN-3 is a Autotaxin(ATX) inhibitor with an IC50 of 2.4 nM, compound 33, sourced from patent WO2018212534A1[1].

  • CAS Number: 2156655-68-2
  • MF: C22H21N9O2
  • MW: 443.46
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.482±0.06 g/cm3(Predicted)
  • Boiling Point: 807.6±75.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

GF109

GF109 is a potent parenteral inhibitor of angiotensin converting enzyme (ACE). GF109 has antihypertensive effects[1].

  • CAS Number: 79873-93-1
  • MF: C10H12F2N4O2
  • MW: 258.22500
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.52g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Homo-PROTAC cereblon degrader 1

Homo-PROTAC cereblon degrader 1 (compound 15a) is a highly potent and efficient cereblon (CRBN) degrader with only minimal effects on IKZF1 and IKZF3[1].

  • CAS Number: 2244520-98-5
  • MF: C32H32N6O10
  • MW: 660.63
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lonodelestat

Lonodelestat (POL6014) is a potent, orally active and selective peptide inhibitor of human neutrophil elastase (hNE)[1][2].

  • CAS Number: 906547-89-5
  • MF: C71H111N15O19
  • MW: 1478.73
  • Catalog: Elastase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 1750.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1012.3±34.3 °C

A-9758

A-9758 is a RORγ ligand and a potent, selective RORγt inverse agonist (IC50=5 nM), and exhibits robust potency against IL-17A release. A-9758 is effective in suppressing both Th17 differentiation and Th17 effector function. A-9758 significantly attenuates IL-23 driven psoriasiform dermatitis and is effective in blocking skin and joint inflammation[1].

  • CAS Number: 2055271-22-0
  • MF: C25H23Cl2F3N2O3
  • MW: 527.36
  • Catalog: Interleukin Related
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NCT-501

NCT-501 is a potent and selective theophylline-based inhibitor of aldehyde dehydrogenase 1A1 (ALDH1A1), inhibits hALDH1A1 with IC50 of 40 nM, typically shows better selectivity over other ALDH isozymes and other dehydrogenases (hALDH1B1, hALDH3A1, and hALDH2, IC50 >57 μM).IC50 value: 40 nMTarget: hALDH1A11) NCT-501 is well absorbed and distributed but rapidly metabolized and/or excreted. NCT-501 does penetrate the blood-brain barrier.2) NCT-501(ALDH1A1 inhibitor) inhibited functional properties, such as self-renewal property, migratory potential and induced sell sensitivity in cisplatin resistant cells. In all, NCT-501 in combination with Cisplatin showed a significant decrease in proliferating cells as compared to individual treatment.You can use NCT-501 (20nM)+ Cisplatin (5 M) to investigate the functional properties.[2]

  • CAS Number: 1802088-50-1
  • MF: C21H32N6O3
  • MW: 416.517
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 627.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 333.2±34.3 °C

CHK-336

CHK-336 (Example 1) is an orally active LDHA inhibitor (IC50<1 nM) that inhibits lactate production in mouse hepatocytes. CHK-336 can be used in the study of hyperoxaluria[1].

  • CAS Number: 2743436-86-2
  • MF: C24H20F2N4O4S2
  • MW: 530.57
  • Catalog: Lactate Dehydrogenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Z-Phe-Phe-diazomethylketone

Z-Phe-Phe-Diazomethylketone is a selective inhibitor of cathepsin L[1].

  • CAS Number: 65178-14-5
  • MF: C27H26N4O4
  • MW: 470.52000
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Enasidenib mesylate

Enasidenib mesylate is a first-in-class, oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes.

  • CAS Number: 1650550-25-6
  • MF: C20H21F6N7O4S
  • MW: 569.481
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bergapten-d3

Bergapten-d3 is deuterium labeled Bergapten. Bergapten is a natural anti-inflammatory and anti-tumor agent. Bergapten is inhibitory towards mouse and human CYP isoforms.

  • CAS Number: 2749409-59-2
  • MF: C12H5D3O4
  • MW: 219.21
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Saikosaponin A

Saikosaponin A is an active component of Bupleurum falcatum, up-regulates LXRα expression, with potent anti-inflammatory activity[1].

  • CAS Number: 20736-09-8
  • MF: C42H68O13
  • MW: 780.982
  • Catalog: LXR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 893.7±65.0 °C at 760 mmHg
  • Melting Point: 225 - 235ºC
  • Flash Point: 494.3±34.3 °C

MY33-3 (hydrochloride)

MY33-3 hydrochloride is a potent and selective inhibitor of receptor protein tyrosine phosphatase (RPTP)β/ζ, with an IC50 of ~0.1 μM. MY33-3 hydrochloride also inhibits PTP-1B (IC50 ~0.7 μM). MY33-3 hydrochloride can reduce ethanol consumption and alleviate Sevoflurane-induced neuroinflammation and cognitive dysfunction[1][2][3].

  • CAS Number: 2204280-42-0
  • MF: C16H14ClF6NS2
  • MW: 433.86
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Heat Shock Protein Inhibitor II

KNK423 is a specific heat shock protein (HSP) synthesis inhibitor. KNK423 improves the efficiency of Amphotericin B in inhibiting resistant Aspergillus terreus by blocking HSP70. KNK423 can be used in cancer and bacterial infection research[1][2].

  • CAS Number: 1859-42-3
  • MF: C12H11NO3
  • MW: 217.22
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DHODH-IN-4

DHODH-IN-4 (compound 17) is a human and Plasmodium falciparum dihydroorotate dehydrogenase (DHODH) inhibitor, with IC50 values of 4 μM and 0.18 μM for PfDHODH and HsDHODH, respectively. DHODH-IN-4 (compound 17) possess antimalarial activity[1].

  • CAS Number: 1148125-93-2
  • MF: C17H12Cl2N2O2
  • MW: 347.20
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zofenopril calcium

Zofenopril Calcium(SQ26991) is an antioxidant that acts as an angiotensin-converting enzyme inhibitor.Target: ACEZofenopril is a pro-drug designed to undergo metabolic hydrolysis yielding the active free sulfhydryl compound zofenoprilat, which is an angiotensin converting enzyme (ACE) inhibitor [1]. Zofenopril promotes the regeneration of peripheral nerve injuries in rat models [2]. Zofenopril increases SR calcium cycling and stimulates active calcium uptake into the SR [3].

  • CAS Number: 81938-43-4
  • MF: C22H22Ca0.5NO4S2
  • MW: 448.58
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.34 g/cm3
  • Boiling Point: 646.3ºC at 760 mmHg
  • Melting Point: >250ºC
  • Flash Point: 344.7ºC

PHD-IN-2

PHD-IN-2 (Compound 91) is a PHD antagonist (IC50: < 5 nM). PHD-IN-2 induces erythropoietin synthesis in HEP3B cells (EC50: <2.5 μM). PHD-IN-2 can be used for research of cardiovascular disorders, metabolic disorders, hematological disorders, pulmonary disorders, kidney disorders, liver disorders, wound healing disorders, and cancer[1].

  • CAS Number: 2924182-42-1
  • MF: C26H27N7O4
  • MW: 501.54
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A