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.


Anti-infection >
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Apoptosis >
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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
Neuronal Signaling >
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NF-κB >
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Protein Tyrosine Kinase/RTK >
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VD/VDR
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Hydroxyevodiamine

Hydroxyevodiamine (Rhetsinine) inhibits aldose reductase with an IC50 value of 24.1 μM[1].

  • CAS Number: 1238-43-3
  • MF: C19H17N3O2
  • MW: 319.357
  • Catalog: Aldose Reductase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 633.4±55.0 °C at 760 mmHg
  • Melting Point: 190 °C
  • Flash Point: 336.9±31.5 °C

ER 50891

ER-50891 is a potent antagonist of retinoic acid receptor α(RARα). ER-50891 significantly attenuates ATRA's inhibitive effects on BMP 2-induced osteoblastogenesis[1].

  • CAS Number: 187400-85-7
  • MF: C29H24N2O2
  • MW: 432.51300
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hCAIX/XII-IN-2

hCAIX/XII-IN-2 (compound 6a) is a potent and selective hCAIX and hCAXIIinhibitor with Ki values of >10000, >10000, 30.0, 3.6 nM for hCAI, hCAII, hCAIX and hCAXII, respectively[1].

  • CAS Number: 2414629-82-4
  • MF: C19H14N2O4
  • MW: 334.33
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trandolaprilat Monohydrate

Trandolaprilate hydrate is a potent angiotensin-converting enzyme (ACE) inhibitor. Trandolaprilate hydrate partially inhibits angiotensin-I-mediated c-fos induction. Trandolaprilate is main bioactive metabolite of Trandolapril. Trandolaprilate shows high lipophilicity[1][2].

  • CAS Number: 951393-55-8
  • MF: C22H32N2O6
  • MW: 420.49900
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

K 579

K579 is a potent and orally active dipeptidyl peptidase IV inhibitor. K579 inhibits the blood glucose elevation. K579 increases the plasma insulin and active forms of glucagon-like peptide-1 (GLP-1). K579 has the potential for the research of diabetic[1].

  • CAS Number: 440100-64-1
  • MF: C17H24N6O
  • MW: 328.41
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

metyrapone

Metyrapone is an inhibitor of cytochrome P450-mediated ω/ω-1 hydroxylase activity and CYP11B1.Target: CYP11B1Metyrapone is a drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism). Metyrapone blocks cortisol synthesis by reversibly inhibiting steroid 11β-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11-Deoxycortisol levels.

  • CAS Number: 54-36-4
  • MF: C14H14N2O
  • MW: 226.274
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 384.4±22.0 °C at 760 mmHg
  • Melting Point: 53-56ºC
  • Flash Point: 189.3±28.8 °C

BIIB021

BIIB021 is an orally available, fully synthetic inhibitor of HSP90 with Ki and EC50 of 1.7 nM and 38 nM, respectively.

  • CAS Number: 848695-25-0
  • MF: C14H15ClN6O
  • MW: 318.762
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 588.5±60.0 °C at 760 mmHg
  • Melting Point: 192-193℃
  • Flash Point: 309.7±32.9 °C

Glycerol trimyristate

Trimyristin, an active molluscicidal component of Myristica fragrans Houtt, significantly inhibits acetylcholinesterase (AChE), acid and alkaline phosphatase (ACP/ALP) activities in the nervous tissue of Lymnaea acuminata. IC50s of Trimyristin against AChE, ACP, and ALP are 0.11, 0.16 and 0.18 mM, respectively[1].

  • CAS Number: 555-45-3
  • MF: C45H86O6
  • MW: 723.161
  • Catalog: Phosphatase
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 703.5±27.0 °C at 760 mmHg
  • Melting Point: 56-57 °C(lit.)
  • Flash Point: 270.9±23.8 °C

Anticancer agent 143

Anticancer agent 143 (compound 369) is a dual PTPN2/PTP1B inhibitor with IC50 values <2.5 nM. Anticancer agent 143 can be used in cancer research[1].

  • CAS Number: 2948339-38-4
  • MF: C19H15BrF2N3O6PS2
  • MW: 594.34
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Olprinone

Olprinone(Loprinone) is a selective phosphodiesterase 3 (PDE3) inhibitor. IC50 value:Target: PDE3Olprinone is used as cardiotonic agent with positive inotropic and vasodilating effects. Olprinone has been reported to improve microcirculation and attenuate inflammation. Olprinone is often used to increase cardiac output after cardiopulmonary bypass (CPB). Olprinone was infused at a rate of 0.2 μg/kg/min when weaning from CPB was started. Olprinone has also shown potent antioxidative and anti-inflammatory effects in the meconium-induced oxidative lung injury.

  • CAS Number: 106730-54-5
  • MF: C14H10N4O
  • MW: 250.255
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: >300ºC
  • Flash Point: N/A

SDZ-MKS 492

SDZ-MKS 492 (MKS 492) is a selective type III isozyme inhibitor of cyclic nucleotide phosphodiesterase, effective in allergic bronchoconstriction and platelet activating factor (PAF) or LTB4-induced inflammatory reactions in animals[1].

  • CAS Number: 114606-56-3
  • MF: C20H27N5O6
  • MW: 433.46
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DHODH-IN-3

DHODH-IN-3 (compound 3) is a potent inhibitor of Human Dihydroorotate Dehydrogenases (HsDHODH) with an IC50 value of 261 nM. DHODH-IN-3 binds to the the ubiquinone binding cavities in DHODH with a Kiapp of 32 nM. DHODH-IN-3 has the potential for malaria treatment[1].

  • CAS Number: 1148126-04-8
  • MF: C17H13ClN2O2
  • MW: 312.75
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isoglycycoumarin

Isoglycycoumarin is a flavonoid isolated from the roots of Glycyrrhiza uralensis. Isoglycycoumarin is a highly selective probe for human cytochrome P450 2A6 (CYP2A6)[1][2].

  • CAS Number: 117038-82-1
  • MF: C21H20O6
  • MW: 368.38000
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JE-2147

JE-2147 (AG1776) is a potent dipeptide protease inhibitor with a Ki of 0.33 nM for HIV-1 protease. JE-2147 has effective activities against a wide spectrum of HIV-1, HIV-2, simian immunodeficiency virus, and various clinical HIV-1 strains in vitro[1][2].

  • CAS Number: 186538-00-1
  • MF: C32H37N3O5S
  • MW: 575.71800
  • Catalog: HIV
  • Density: 1.258g/cm3
  • Boiling Point: 861.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 474.8ºC

PTP1B-IN-8

PTP1B-IN-8 is a potent and selective potent protein tyrosine phosphatase-1B (PTP1B) inhibitor extracted from patent CN103626692A, example 1[1].

  • CAS Number: 919091-61-5
  • MF: C19H13Cl4NO
  • MW: 413.12
  • Catalog: Phosphatase
  • Density: 1.463±0.06 g/cm3(Predicted)
  • Boiling Point: 607.5±55.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Aloin

Aloin (mixture of A&B) is anthraquinone derivative isolated from Aloe vera. Aloin (mixture of A&B) has diverse biological activities such as anti-inflammatory, immunity, antidiabetic, antioxidant, antibacterial, antifungal, and antitumor activities. Aloin (mixture of A&B) also an effective inhibitor of stimulated granulocyte matrix metalloproteinases (MMPs)[1][2].

  • CAS Number: 8015-61-0
  • MF: C21H22O9
  • MW: 418.394
  • Catalog: Bacterial
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 752.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 268.0±26.4 °C

Morin 3-O-β-D-glucopyranoside

Morin 3-O-β-D-glucopyranoside is a natural flavonoid with antifungal, anticancer and antioxidant activities. Morin 3-O-β-D-glucopyranoside inhibits reverse transcriptase, protein-tyrosine kinase and xanthine oxidase, and also shows anti-HIV, antiarteriosclerotic, and superoxide scavenging activities[1].

  • Density: 1.87±0.1 g/cm3
  • Boiling Point: 875.2±65.0 °C
  • Melting Point: N/A
  • Flash Point: N/A

TM5441

TM5441 is a plasminogen activator inhibitor-1 (PAI-1); inhibits several tumor cell lines with IC50 values between 9.7 and 60.3 μM.

  • CAS Number: 1190221-43-2
  • MF: C21H17ClN2O6
  • MW: 428.829
  • Catalog: PAI-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminopeptidase-IN-1

Aminopeptidase-IN-1 (compound 16o) is a potent insulin-regulated aminopeptidase (IRAP) inhibitor with an Ki value of 7.7 μM. Aminopeptidase-IN-1 can be used tor research cognitive and memory impairments[1].

  • CAS Number: 374102-08-6
  • MF: C18H16N2O6
  • MW: 356.33
  • Catalog: Aminopeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PFKFB3-IN-2

PFKFB3-IN-2 is a 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) inhibitor. PFKFB3-IN-2 has potential applications in cancer, neurodegenerative diseases, autoimmune diseases, inflammatory diseases, multiple sclerosis, metabolic diseases, angiogenesis inhibition and other diseases[1].

  • CAS Number: 794552-84-4
  • MF: C14H11NO7S
  • MW: 337.30
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-4950834

PF-4950834 is a potent, selective, orally bioavailable, ATP-competitive rho kinase inhibitor with IC50 values of 8.35 nM and 33.12 nM against ROCK2 and ROCK1, respectively. PF-4950834 inhibits neutrophil migration[1].

  • CAS Number: 1256264-62-6
  • MF: C21H19N3O2
  • MW: 345.39
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-03049423

PF-03049423 is a potent, selective, orally active, and brain penetrant inhibitor of PDE5 with IC50 of 0.2 nM; displays 158-fold and 2460-fold selectivity over PDE6 and PDE11, respectively; possesses an excellent potency and selectivity profile and demonstrates robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Stroke Phase 2 Discontinued

  • CAS Number: 402955-58-2
  • MF: C24H32N6O4
  • MW: 505.010
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyr-Phe

H-Tyr-Phe-OH (L-Tyrosyl-L-phenylalanine) is an orally active inhibitor of Angiotensin converting enzyme (ACE), with an inhibiton rate of 48% at 50 μM. H-Tyr-Phe-OH can be used as an biomarker for differentiating benign thyroid nodules (BTN) from thyroid cancer (TC). H-Tyr-Phe-OH exhibits xanthine oxidase inhibition (uric acid lowering) activity and serves as regulator in IL-8 production in neutrophil-like cells[1][2][3][4].

  • CAS Number: 17355-11-2
  • MF: C18H20N2O4
  • MW: 328.36200
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.3 g/cm3
  • Boiling Point: 642.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 342.2ºC

Cordycepin

Cordycepin, which is a nucleoside derivative isolated from Cordyceps, inhibits IL-1β-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts (RASFs) in a dose-dependent manner.

  • CAS Number: 73-03-0
  • MF: C10H13N5O3
  • MW: 251.242
  • Catalog: MMP
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 627.2±65.0 °C at 760 mmHg
  • Melting Point: 225-229ºC
  • Flash Point: 333.1±34.3 °C

edaravone

Edaravone is a strong novel free radical scavenger, and inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator.

  • CAS Number: 89-25-8
  • MF: C10H10N2O
  • MW: 174.199
  • Catalog: MMP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 333.0±11.0 °C at 760 mmHg
  • Melting Point: 126-128 °C(lit.)
  • Flash Point: 155.2±19.3 °C

DMU2139(CYP1B1 inhibitor 6j)

DMU2139 is a potent and specific CYP1B1 inhibitor, with IC50s of 9 nM and 795 nM for CYP1B1 and CYP1A1, respectively.

  • CAS Number: 1821143-80-9
  • MF: C19H15NO2
  • MW: 289.33
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bezeparsen

Bezeparsen is a PCSK9 synthesis inhibitor[1].

  • CAS Number: 2639640-84-7
  • MF: C238H335N67O113P16S15
  • MW: 6919.13
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GW280264X

GW280264X is the mixed ADAM10/TACE (ADAM17) metalloproteinases inhibitor. GW280264X potently blocks TACE (ADAM17) and ADAM10 with IC50s of 8.0 nM and 11.5 nM, respectively[1]. ADAM10 and 17 modulate the immunogenicity of glioblastoma-initiating cells[2].

  • CAS Number: 866924-39-2
  • MF: C28H41N5O6S
  • MW: 575.72
  • Catalog: MMP
  • Density: 1.229±0.06 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Atorvastatin hemicalcium trihydrate

Atorvastatin hemicalcium trihydrate is an orally active HMG-CoA reductase inhibitor, has the ability to effectively decrease blood lipids. Atorvastatin hemicalcium trihydrate inhibits human SV-SMC proliferation and invasion with IC50s of 0.39 μM and 2.39 μM, respectively[1][2][3].

  • CAS Number: 344920-08-7
  • MF: C33H35FN2O5.1/2Ca.3H2O
  • MW: 632.73
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP145

MMP145 (compound 27) is a potent, selective and orally active MMP-12 inhibitor. MMP145 is effective in inflammation and asthma reasearch[1].

  • CAS Number: 1025717-75-2
  • MF: C20H20N2O7S
  • MW: 432.44700
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A