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 >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
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Apoptosis >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
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Metabolic Enzyme/Protease >
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 >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
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Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
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XMD 8-87

XMD8-87 is a potent TNK2 inhibitor with IC50 values of 38 and 113 nM for the D163E and R806Q mutations, respectively.

  • CAS Number: 1234480-46-6
  • MF: C24H27N7O2
  • MW: 445.517
  • Catalog: Tyrosinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GlcN-6-P Synthase-IN-1

GlcN-6-P Synthase-IN-1 (Compound 4d) is a Glucosamine-6-phosphate (GlcN-6-P) synthase inhibitor with an IC50 of 3.47 μM. GlcN-6-P Synthase-IN-1 exhibits significant antimicrobial activity. GlcN-6-P Synthase-IN-1 has good penetration in the CNS and is able to inhibit the cytochrome P450, CYP3A4 isoform[1].

  • CAS Number: 2447602-44-8
  • MF: C20H21N7S
  • MW: 391.49
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD 3988

AZD3988 is a diacylglycerol acyl transferase-1 (DGAT-1) inhibitor with IC50s of 6, 5, 11 nM for human, rat, mouse, respectively[1].

  • CAS Number: 892489-52-0
  • MF: C23H22F2N4O4
  • MW: 456.44
  • Catalog: Acyltransferase
  • Density: 1.402
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FAAH inhibitor 1

FAAH inhibitor 1 is a potent fatty acid amide hydrolase (FAAH) inhibitor with an IC50 of 18±8 nM.IC50 Value: 18±8 nM [1]Target: FAAHTime-dependent preincubation study of FAAH inhibitor 1 was consistent with it being a reversible inhibitor. Activity-based protein-profiling (ABPP) evaluation of FAAH inhibitors 1 in rat tissues revealed that it had exceptional selectivity and no off-target activity with respect to other serine hydrolases. Molecular shape overlay of FAAH inhibitor 1 with a known FAAH inhibitor indicated that these compounds might act as transitionstate analogues, forming putative hydrogen bonds with catalytic residues and mimicking the charge distribution of the tetrahedral transition state. FAAH inhibitors 1 was exclusively specific against FAAH in rat brain and had no missing protein bands in all the other tissues that were tested [1].

  • CAS Number: 326866-17-5
  • MF: C24H23N3O3S3
  • MW: 497.65300
  • Catalog: FAAH
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mca-Tyr-Val-Ala-Asp-Ala-Pro-Lys(Dnp)-OH trifluoroacetate salt

Mca-YVADAP-Lys(Dnp)-OH is a fluorogenic substrate for caspase-1 and angiotensin-converting enzyme 2 (ACE2)[1].

  • CAS Number: 189696-01-3
  • MF: C53H64N10O19
  • MW: 1145.13000
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Torcetrapib

Torcetrapib(CP-529414) is a CETP inhibitor with IC50 of 37 nM, elevates HDL-C and reduces nonHDL-C in plasma.IC50 value: 37 nM [1]Target: CETP inhibitorin vitro: Torcetrapib dose-dependently increases aldosterone release from H295R cells after either 24 or 48 h of treatment with an EC50 of approximately 80 nM, this effect is mediated by calcium channel as calcium channel blockers completely blocks torcetrapib-induced corticoid release and calcium increase. Torcetrapib (1 μM) significantly increases the expression of steroidogenic gene, CYP11B2 and CYP11B1, in H295R cell lines [2].in vivo: Torcetrapib (< 100 mg, daily) changes the plasma distribution of CETP, as the apparent molecular weight of the CETP has shifted to a larger form, by 2 hours after the dose in healthy young subjects. Torcetrapib treatment with 10 mg, 30 mg, 60 mg, and 120 mg daily and 120 mg twice daily results in 16%, 28%, 62%, 73%, and 91% increases in plasma HDL-C, respectively, with no significant changes in TPC in healthy young subjects. [1] Torcetrapib results in an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, in addition to an increase of 5.4 mm Hg in systolic blood pressure, a decrease in serum potassium, and increases in serum sodium, bicarbonate, and aldosterone, in patients at high cardiovascular risk after 12 months' treatment [3]. Torcetrapib (90 mg/kg/day) results in a 70% inhibition of CE transfer in rabbits fed an atherogenic diet. Torcetrapib (90 mg/kg/day) increases mean HDL-C levels by above 3-fold and apoA-I levels by 2.5-fold in plasma in rabbits fed an atherogenic diet. Torcetrapib-treated animal has a multiple-fold increase in HDL-C AUC and a corresponding reduction in aortic lesion area with 60% reduction of aortic free cholesterol (FC) and cholesteryl ester (EC) in rabbits fed an atherogenic diet. Torcetrapib-treated rabbits stimulate free cholesterol efflux to a significantly greater extent than does sera from control rabbits [4].

  • CAS Number: 262352-17-0
  • MF: C26H25F9N2O4
  • MW: 600.47
  • Catalog: CETP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 504.8±50.0 °C at 760 mmHg
  • Melting Point: 54-58ºC
  • Flash Point: 259.1±30.1 °C

FTI-2148

FTI-2148 is a RAS C-terminal mimetic dual farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1) inhibitor with IC50s of 1.4 nM and 1.7 μM for FT-1 and GGT-1, respectively[1].

  • CAS Number: 251577-09-0
  • MF: C24H28N4O3S
  • MW: 452.569
  • Catalog: Farnesyl Transferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 730.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 395.4±32.9 °C

KT182

KT182 is a potent and selective inhibitor of α/β-hydrolase domain containing 6 (ABHD6), with an IC50 of 0.24 nM in Neuro2A cells[1].

  • CAS Number: 1402612-62-7
  • MF: C27H26N4O2
  • MW: 438.52
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAPI-0

TAPI-0 is a TACE (TNF-α converting enzyme; ADAM17) inhibitor with an IC50 of 100 nM. TAPI-0 is a MMP inhibitor and also attenuates TNF-α processing[1][2].

  • CAS Number: 163958-73-4
  • MF: C24H32N4O5
  • MW: 456.53
  • Catalog: Bacterial
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AA38-3

AA38-3 is a serine hydrolase (SH) inhibitor. AA38-3 can inhibit three SHs, ABHD6, ABHD11, and FAAH[1].

  • CAS Number: 65815-76-1
  • MF: C12H14N2O4
  • MW: 250.25
  • Catalog: FAAH
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 397.5±34.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.2±25.7 °C

Anagliptin

Anagliptin is a highly selective, potent inhibitor of dipeptidyl peptidase 4 (DPP-4), with an IC50 of 3.8 nM, and less selective at DPP-8/9 (IC50, 68, 60 nM, respectively).

  • CAS Number: 739366-20-2
  • MF: C19H25N7O2
  • MW: 383.448
  • Catalog: Dipeptidyl Peptidase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ND-322 HCl

ND-322 HCl is a selective inhibitor of MT1-MMP and MMP2 and reduces in vitro melanoma cell growth, migration and invasion.

  • CAS Number: 1333379-23-9
  • MF: C15H16ClNO3S2
  • MW: 357.88
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MJ33

MJ33 is an active-site-directed, specific, competitive, and reversible phospholipase A2 (PLA2) inhibitor. MJ33 blocks the calcium-independent phospholipase A2 (iPLA2) activity of Prdx6[1]. MJ33 has a critical effect on inflammatory brain damage[2].

  • CAS Number: 199106-13-3
  • MF: C22H44F3O7P
  • MW: 498.48300
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: 522.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 269.9ºC

Lopinavir

Lopinavir is a potent HIV protease inhibitor with Ki of 1.3 pM.Target: HIV proteaseLopinavir is a potent inhibitor of Rh123 efflux in Caco-2 monolayers with IC50 of 1.7 mM. Lopinavir exposure (72 hours) in LS 180V cells reduces the content of intracellular Rh123. Lopinavir induces P-glycoprotein immunoreactive protein and messenger RNA levels in LS 180V cells. Lopinavir inhibits subtype C clone C6 with IC50 of 9.4 nM. Lopinavir inhibits CYP3A with IC50 of 7.3 mM in human liver microsomes, while produces negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19 and 2D6. Lopinavir (10 mg/kg, orally) results in Cmax of 0.8 μg/mL and oral bioavailability of 25% in rats.

  • CAS Number: 192725-17-0
  • MF: C37H48N4O5
  • MW: 628.801
  • Catalog: HIV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 924.2±65.0 °C at 760 mmHg
  • Melting Point: 124-127°C
  • Flash Point: 512.7±34.3 °C

SR2211

SR2211 is a potent, selective synthetic RORγ modulator and functions as an inverse agonist, with a Ki of 105 nM and an IC50 of ~320 nM.

  • CAS Number: 1359164-11-6
  • MF: C26H24F7N3O
  • MW: 527.477
  • Catalog: ROR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 552.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 287.9±30.1 °C

lithium,[(3aS,5aR,8aR,8bS)-2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydrodi[1,3]dioxolo[4,5-a:5',3'-d]pyran-3a-yl]methoxysulfonylazanide

Topiramate (McN 4853) lithium is a broad-spectrum antiepileptic agent. Topiramate lithium is a GluR5 receptor antagonist. Topiramate produces its antiepileptic effects through enhancement of GABAergic activity, inhibition of kainate/AMPA receptors, inhibition of voltage-sensitive sodium and calcium channels, increases in potassium conductance, and inhibition of carbonic anhydrase[1][2][3].

  • CAS Number: 488127-53-3
  • MF: C12H20LiNO8S
  • MW: 345.29500
  • Catalog: Calcium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bradykinin Potentiator C

Bradykinin potentiator C is a potent angiotensin-converting enzyme (ACE) inhibitor with an IC50 of 7.1 μM for rabbit lung ACE. Bradykinin potentiator C is a postulated prototype of functional peptide[1].

  • CAS Number: 30953-20-9
  • MF: C51H77N11O13
  • MW: 1052.22000
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Quinapril hydrochloride

Quinapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications.Target: ACEQuinapril is an angiotensin-converting enzyme inhibitor (ACE inhibitor) used in the treatment of hypertension and congestive heart failure. Quinapril is rapidly de-esterified after absorption to quinaprilat (the active diacid metabolite), a potent angiotensin converting enzyme (ACE) inhibitor. Quinapril is now firmly established as an effective and well tolerated ACE inhibitor for the treatment of patients with hypertension and congestive heart failure. Quinapril 40 mg/day also significantly reduced the incidence of ischaemic events in patients undergoing CABG in one study [1, 2]. An overview of 32 clinical trials of ACE inhibitors in heart failure showed that no significant heterogeneity in mortality was found among enalapril, ramipril, quinapril, captopril, lisinopril, benazepril, perindopril and cilazapril. Initiation of therapy with captopril, ramipril, and trandolapril at least 3 days after an acute MI resulted in all-cause mortality risk reductions of 18 to 27% [3].

  • CAS Number: 82586-55-8
  • MF: C25H31ClN2O5
  • MW: 474.977
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: 662ºC at 760 mmHg
  • Melting Point: 120-130ºC
  • Flash Point: 354.1ºC

3,4-Dichloro-isocoumarin

3,4-Dichloroisocoumarin is a potent serine-protease inhibitor that inhibits chymotrypsin-like activity[1].

  • CAS Number: 51050-59-0
  • MF: C9H4Cl2O2
  • MW: 215.03300
  • Catalog: Ser/Thr Protease
  • Density: 1.53 g/cm3
  • Boiling Point: 304.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 136.6ºC

Quilseconazole

Quilseconazole (VT-1129) is a potent, orally active fungal Cyp51 (lanosterol 14-α-demethylase) inhibitor, binds tightly to cryptococcal CYP51, but weakly inhibits humans CYP450 enzymes[1].

  • CAS Number: 1340593-70-5
  • MF: C22H14F7N5O2
  • MW: 513.37
  • Catalog: Fungal
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SC-43

SC-43, a Sorafenib derivative, is a potent and orally active SHP-1 (PTPN6) agonist. SC-43 inhibits the phosphorylation of STAT3 and induces cell apoptosis. SC-43 has anti-fibrotic and anticancer effects[1][2].

  • CAS Number: 1400989-25-4
  • MF: C21H13ClF3N3O2
  • MW: 431.80
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HLI-98C

HLI98C is a ubiquitin ligase inhibitor. HLI98C inhibits p53 ubiquitylation. HLI98C inhibits HDM2 auto-ubiquitylation[1].

  • CAS Number: 317326-90-2
  • MF: C17H9ClN4O4
  • MW: 368.73100
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydromorin

Dihydromorin, a natural flavanonol compound, is a tyrosinase inhibitor[1].

  • CAS Number: 18422-83-8
  • MF: C15H12O7
  • MW: 304.252
  • Catalog: Tyrosinase
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 693.8±55.0 °C at 760 mmHg
  • Melting Point: 224°C (lit.)
  • Flash Point: 266.5±25.0 °C

CB 300919

CB 300919 is a water-soluble analogue of CB30865; has a continuous exposure (96 h) growth inhibition IC50 value of 2 nM in human CH1 ovarian tumor xenograft.IC50 value:Target: Nampt

  • CAS Number: 289715-28-2
  • MF: C32H34ClN7O2
  • MW: 584.11100
  • Catalog: Nampt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Darunavir Ethanolate

Darunavir ethanolate (TMC114 ethanolate) is a potent HIV protease inhibitor used to treat and prevent HIV/AIDS. Darunavir has a Ki of 1 nM for wild type HIV-1 protease.

  • CAS Number: 635728-49-3
  • MF: C29H43N3O8S
  • MW: 593.732
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Diaminopropionoyl tripeptide-33

Diaminopropionoyl tripeptide-33isa bioactive peptide with protects skin cells from UVA-induced DNA damages and has been reported used as a cosmetic ingredient[1].

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

(+)-Mediresinol Di-O-beta-D-glucopyranoside

(+)-Medioresinol Di-O-β-D-glucopyranoside is a lignan glucoside with strong inhibitory activity of 3', 5'-cyclic monophosphate (cyclic AMP) phosphodiesterase[1].

  • CAS Number: 88142-63-6
  • MF: C33H44O17
  • MW: 712.69
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Diosmetin

Diosmetin is a natural flavonoid which inhibits human CYP1A enzyme activity with an IC50 of 40 μM in HepG2 cell.

  • CAS Number: 520-34-3
  • MF: C16H12O6
  • MW: 300.263
  • Catalog: Cytochrome P450
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 576.7±50.0 °C at 760 mmHg
  • Melting Point: 256-258ºC
  • Flash Point: 220.3±23.6 °C

(3S,5S)-Atorvastatin

(3S,5S)-Atorvastatin is a inactive enantiomer of Atorvastatin. (3S,5S)-Atorvastatin can activate pregnane X receptor (PXR). Atorvastatin is an orally active HMG-CoA reductase inhibitor, has the ability to effectively decrease blood lipids[1][2].

  • CAS Number: 501121-34-2
  • MF: C33H35FN2O5
  • MW: 558.64000
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 182-184ºC
  • Flash Point: N/A

Carbonic anhydrase inhibitor 7

Carbonic anhydrase inhibitor 7 (compound 5b) is a potent inhibitor of human carbonic anhydrase (hCA), with Kis of 6.5 nM, 7.1 nM, 72.1 nM, and 255.8 nM for hCA IX, hCA II, hCA XII and hCA I, respectively[1].

  • CAS Number: 546105-61-7
  • MF: C23H17N3O5S
  • MW: 447.46
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A