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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AC 55649

AC-55649 is a potent, highly isoform-selective agonist of human RARβ2 receptor, with a pEC50 of 6.9.

  • CAS Number: 59662-49-6
  • MF: C21H26O2
  • MW: 310.43000
  • Catalog: RAR/RXR
  • Density: 1.037g/cm3
  • Boiling Point: 462ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 216.9ºC

PT-2385

PT-2385 is a selective HIF-2α antagonist with a Ki of less than 50 nM.

  • CAS Number: 1672665-49-4
  • MF: C17H12F3NO4S
  • MW: 383.342
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 524.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 271.1±30.1 °C

beta-Rhamnocitrin

Rhamnetin is a quercetin derivative found in Coriandrum sativum, inhibits secretory phospholipase A2, with antioxidant and anti-inflammatory activity[1].

  • CAS Number: 90-19-7
  • MF: C16H12O7
  • MW: 316.26200
  • Catalog: Phospholipase
  • Density: 1.634g/cm3
  • Boiling Point: 627.9ºC at 760 mmHg
  • Melting Point: 293-296°C (dec.)
  • Flash Point: 238.9ºC

N(alpha)-acetylglycyllysyl methyl ester

Ac-Gly-Lys-OMe is a substrate for urokinase. Ac-Gly-Lys-OMe can be used to measure the effects of small molecule inhibitors on urokinase activity[1].

  • CAS Number: 10236-44-9
  • MF: C13H25N3O6
  • MW: 319.354
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAY-60-7550

Bay 60-7550 is a potent and selective PDE2 inhibitor with a Ki of 3.8 nM.

  • CAS Number: 439083-90-6
  • MF: C27H32N4O4
  • MW: 476.56700
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SPC4061

SPC4061 an antisense nucleotide, is a potent PCSK9 inhibitor. SPC4061 targets the lock-in nucleic acid (LNA) of PCSK9 for the study of hypercholesterolemia and related diseases[1][2].

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

3-O-Ethyl-L-ascorbic acid

3-O-Ethyl-L-ascorbic acid, a stable vitamin C derivative, is a cosmetic tyrosinase tnhibitor with a whitening capacity. 3-O-Ethyl-L-ascorbic acid also has antioxidant abilities[1][2].

  • CAS Number: 86404-04-8
  • MF: C8H12O6
  • MW: 204.177
  • Catalog: Tyrosinase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 551.5±50.0 °C at 760 mmHg
  • Melting Point: 112.0 to 116.0 °C
  • Flash Point: 228.5±23.6 °C

NIC-0102

NIC-0102 is an orally active proteasome inhibitor (pIC50=7.55) that specifically inhibits NLRP3 inflammatory vesicle activation. NIC-0102 shows potent anti-inflammatory effects in a model of dextran sulfate sodium (DSS)-induced ulcerative colitis. NIC-0102 also inhibits production of pro-IL-1β[1].

  • CAS Number: 2806031-94-5
  • MF: C21H25BF2N2O4
  • MW: 418.24
  • Catalog: NOD-like Receptor (NLR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dual FAAH/sEH-IN-1

Dual FAAH/sEH-IN-1 (compound 3) is a high affinity dual sEH (soluble epoxide hydrolase) and FAAH (fatty acid amide hydrolase) inhibitor, with IC50 values of 9.6 and 7 nM, respectively. Dual FAAH/sEH-IN-1 shows antinociception against the inflammatory phase[1].

  • CAS Number: 2756099-59-7
  • MF: C25H22ClN3O3S2
  • MW: 512.04
  • Catalog: FAAH
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pravastatin

Pravastatin is an HMG-CoA reductase inhibitor against sterol synthesis with IC50 of 5.6 μM.Target: HMG-CoA reductasePravastatin (marketed as Pravachol or Selektine) is a member of the drug class of statins, used in combination with diet, exercise, and weight-loss for lowering cholesterol and preventing cardiovascular disease.Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease. It is recommended to be used only after other measures such as diet, exercise, and weight reduction have not improved cholesterol levels.The evidence for the use of pravastatin is generally weaker than for other statins. The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT), failed to demonstrate a difference in all-cause mortality or nonfatal myocardial infarction/fatal coronary heart disease rates between patients receiving pravastatin 40mg daily (a common starting dose) and those receiving usual care.

  • CAS Number: 81093-37-0
  • MF: C23H36O7
  • MW: 424.53
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 634.5±55.0 °C at 760 mmHg
  • Melting Point: 171.2-173ºC
  • Flash Point: 213.2±25.0 °C

FAS-IN-1

FAS-IN-1 is a potent inhibitor of Fatty acid synthase (FAS) wtih IC50 of 10 nM, extracted from Patnet WO2012/064642Al.

  • CAS Number: 1375105-96-6
  • MF: C26H27N3O4S
  • MW: 477.57500
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LG100268

LG100268 (LG268) is a potent, selective and orally active retinoid X receptor (RXR) agonist with EC50 values of 4 nM, 3 nM, and 4 nM for RXR-α, RXR-β, and RXR-γ, respectively[1]. LG100268 displays >1000-fold selectivity for RXR over RAR, the Ki values are 3.4 nM, 6.2 nM and 9.2 nM for RXR-α, RXR-β, and RXR-γ, respectively[2]. LG100268 activates RXR homodimers to induce transcriptional activation. LG100268 can be used for the study of lung carcinogenesisy[3].

  • CAS Number: 153559-76-3
  • MF: C24H29NO2
  • MW: 363.49300
  • Catalog: Autophagy
  • Density: 1.115g/cm3
  • Boiling Point: 487ºC at 760mmHg
  • Melting Point: 275-277ºC
  • Flash Point: 248.3ºC

Enpp-1-IN-6

Enpp-1-IN-6 is a potent inhibitor of ectonucleotide pyrophosphatase-phosphodiesterase 1 (enpp-1). The ENPP 1 has broad specificity and can cleave a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds nucleotides and nucleotide sugars. Enpp-1-IN-6 has the potential for the research of cancer and infectious diseases (extracted from patent WO2021203772A1, compound 51)[1].

  • CAS Number: 2718971-29-8
  • MF: C22H28N4O5S
  • MW: 460.55
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IS-741

Fuzapladib (IS-741) is a potent phospholipase A2 inhibitor. Fuzapladib can block the adhesion of inflammatory cells to microvascular endothelial cells, inhibit the infiltration of neutrophils into the pancreas or acute pancreatitis, and has anti-acute pancreatitis effects[1].

  • CAS Number: 141283-87-6
  • MF: C15H20F3N3O3S
  • MW: 379.39800
  • Catalog: Phospholipase
  • Density: 1.411g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fasnall

Fasnall is a selective fatty acid synthase (FASN) inhibitor with an IC50 of 3.71 μM. Fasnall induces apoptosis in HER2+ breast cancer cell lines. Fasnall shows potent anti-tumor activities[1].

  • CAS Number: 929978-58-5
  • MF: C19H22N4S
  • MW: 338.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hinnuliquinone

Hinnuliquinone is a C2-symmetric dimeric non-peptide fungal metabolite inhibitor of HIV-1 protease. Hinnuliquinone is a bis-indolyl-2,5-dihydroxybenzoquinone pigment, that can be isolated from Nodulisphorium hinnuleum[1][2].

  • CAS Number: 78860-37-4
  • MF: C32H30N2O4
  • MW: 506.59200
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thrombin inhibitor 1

Thrombin inhibitor 1 is a potent thrombin inhibitor (Ki=0.66 nM, 2xaPTT=0.43 μM).

  • CAS Number: 855998-46-8
  • MF: C22H20Cl2F2N4O3
  • MW: 497.32
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKB-6899

AKB-6899, a prolyl hydroxylase domain 3 (PHD3) inhibitor, is a selective HIF-2α stabilizer. AKB-6899 also increases soluble form of the VEGF receptor (sVEGFR-1) production from GM-CSF-treated macrophages, and has antitumor and antiangiogenic effects[1].

  • CAS Number: 1007377-55-0
  • MF: C14H11FN2O4
  • MW: 290.25
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

27-Hydroxycholesterol

27-Hydroxycholesterol is a selective estrogen receptor modulator and an agonist of the liver X receptor.

  • CAS Number: 20380-11-4
  • MF: C27H46O2
  • MW: 402.653
  • Catalog: LXR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 517.1±23.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 215.6±17.2 °C

Liarozole dihydrochloride

Liarozole dihydrochloride (R75251; R85246) is a cytochrome P450 (CYP450) dependent inhibitor, orally active, it also a potent inhibitor of estrogen (via inhibition of aromatase) and testicular androgen synthesis (inhibition of 17 ,20-lyase). Liarozole dihydrochloride prevents the catabolism of retinoic acid via inhibition of 4-hydroxylase and exhibits retinoid sparing and retinoid-mimetic effects in vivo. Liarozole dihydrochloride is an imidazole derivative; it is being investigated as a non-hormonal agent in prostate cancer and in the treatment of various other cancers and skin disorders[1].

  • CAS Number: 1883548-96-6
  • MF: C17H15Cl3N4
  • MW: 381.69
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isotretinoin

Isotretinoin(13-cis-Retinoic acid) is a medication used for the treatment of severe acne. It was first developed to be used as a chemotherapy medication for the treatment of brain cancer, pancreatic cancer and more.Target: RAR/RXRIsotretinoin has been the most effective and long-lasting drug for the treatment of severe acne for more than 30 years and can achieve long-term remission in 70-80% of patients after a single course. The new evidence-based European S3-guideline recommends the use of Isotretinoin as a first-line medication for the treatment of severe papulopustular or conglobate acne, especially when prognostically unfavorable factors are present: family history of acne, early onset, marked seborrhea, localization on the trunk, scarring, psychosocial disability or persistent/late-type acne [1]. Five patients with pityriasis rubra pilaris were treated with isotretinoin from September 1982 through 1985. Isotretinoin at an average dose of 1.16 mg/kg/day for 16 to 24 weeks caused complete or almost complete clearing in four of the five patients [2]. isotretinoin produces significant anti-inflammatory effects by inhibition of monocyte and neutrophil chemotaxis across intact biologic barriers in vivo [3]. Isotretinoin 5 mg/day is effective in reducing the number of acne lesions, and improving patients dermatologic quality of life, with minimal adverse effects [4]. Clinical indications: Acne Toxicity: Isotretinoin is teratogenic. It also causes mucocutaneous side effects suck as cheilitis, dry skin, and dry eyes.

  • CAS Number: 4759-48-2
  • MF: C20H28O2
  • MW: 300.435
  • Catalog: RAR/RXR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 462.8±14.0 °C at 760 mmHg
  • Melting Point: 172-175 °C(lit.)
  • Flash Point: 350.6±11.0 °C

Arbutin

Arbutin(β-Arbutin) is a glycoside; a glycosylated hydroquinone extracted from the bearberry plant in the genus Arctostaphylos; inhibits tyrosinase and thus prevents the formation of melanin.IC50 value:Target: tyrosinase

  • CAS Number: 497-76-7
  • MF: C12H16O7
  • MW: 272.251
  • Catalog: Tyrosinase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 561.6±50.0 °C at 760 mmHg
  • Melting Point: 195-198 °C
  • Flash Point: 293.4±30.1 °C

MG132

(R)-MG-132 is the enantiomer of MG-132. (R)-MG-132 is a proteasome inhibitor[1].

  • CAS Number: 1211877-36-9
  • MF: C26H41N3O5
  • MW: 475.621
  • Catalog: Proteasome
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 682.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 366.3±31.5 °C

LG 100754

LG100754 (UVI 2112) is a RXR dimers modulater. LG100754 acts as a RXR:RXR homodimer antagonist, but functions as a agonist towards RXR:PPARα and RXR:PPARγ heterodimers. LG100754 is an insulin sensitizer that functions through RXR[1].

  • CAS Number: 180713-37-5
  • MF: C26H36O3
  • MW: 396.56200
  • Catalog: RAR/RXR
  • Density: 1.003g/cm3
  • Boiling Point: 549.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 178.5ºC

LY-517717

LY-517717 is a potent and orally active FXa inhibitor. LY-517717 shows antithrombotic and anticoagulant activity. LY-517717 has the potential for the research of venous thromboembolism after hip or knee replacement[1].

  • CAS Number: 313489-71-3
  • MF: C27H33N5O2
  • MW: 459.58300
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JZP 361

JZP-361 is a potent and reversible inhibitor of human recombinant MAGL (hMAGL, IC50=46 nM), and has almost 150-fold higher selectivity over human recombinant fatty acid amide hydrolase (hFAAH, IC50=7.24 μM) and 35-fold higher selectivity over human α/β-hydrolase-6 (hABHD6, IC50=1.79 μM). JZP-361 represents a dual-acting pharmacological tool possessing both MAGL inhibitory and antihistaminergic activities[1].

  • CAS Number: 1680193-80-9
  • MF: C22H20ClN5O
  • MW: 405.880
  • Catalog: Histamine Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 611.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 323.8±34.3 °C

Steppogenin

Steppogenin is a potent inhibitor of HIF-1α and DLL4, with IC50 values of 0.56 and 8.46 μM, respectively. Steppogenin can be sued for the research of angiogenic diseases, such as those involving solid tumors[1].

  • CAS Number: 56486-94-3
  • MF: C15H12O6
  • MW: 288.252
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 631.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 244.2±25.0 °C

8-Geranyloxypsoralen

8-Geranyloxypsoralen is a furanocoumarin isolated from grapefruit, acts as a potent inhibitor of P450 3A4 (CYP3A4) with an IC50 of 3.93 μM[1].

  • CAS Number: 7437-55-0
  • MF: C21H22O4
  • MW: 338.397
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 503.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 258.4±30.1 °C

Autotaxin modulator 1

Autotaxin modulator 1 is a novel Autotaxin modulator extracted from Patent WO 2014018881 A1.

  • CAS Number: 1548743-69-6
  • MF: C28H31F6NO3
  • MW: 543.541
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 586.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.7±30.1 °C

1-(3,4-Dihydroxyphenyl)ethanone

3',4'-Dihydroxyacetophenone (3,4-DHAP), isolated from Picea Schrenkiana Needles exhibits a strong suppressive action against tyrosinase activity, with an IC50 of 10 μM. 3',4'-Dihydroxyacetophenone (3,4-DHAP) is a vasoactive agent and antioxidant[1][2].

  • CAS Number: 1197-09-7
  • MF: C8H8O3
  • MW: 152.147
  • Catalog: Tyrosinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 372.4±27.0 °C at 760 mmHg
  • Melting Point: 117 °C
  • Flash Point: 193.2±20.2 °C