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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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

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

1-Isopropyltryptophan

1-Isopropyltryptophan (1-IsoPT) is a IDO1 inhibitor. 1-Isopropyltryptophan decreases the expression of IFN-γ stimulated ID0-1 and ID0-2 mRNA[1].

  • CAS Number: 1219485-46-7
  • MF: C14H18N2O2
  • MW: 246.30
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PTP1B-IN-9

PTP1B-IN-9 is a ubiquitin-proteasome system (UPS)-stressor. PTP1B-IN-9 inhibits ubiquitin-mediated protein degradation upstream of the 20S proteasomal catalytic activites. PTP1B-IN-9 triggers a ubiquitin-proteasome-system (UPS)-stress response without affecting 20S proteasome catalytic activities. Anticancer activity[1].

  • CAS Number: 145888-79-5
  • MF: C19H13Cl4NO
  • MW: 413.12500
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N6022

N6022 is a potent, selective, reversible, and efficacious S-Nitrosoglutathione reductase(GSNOR) inhibitor with IC50 of 8 nM.

  • CAS Number: 1208315-24-5
  • MF: C24H22N4O3
  • MW: 414.457
  • Catalog: GSNOR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 662.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 354.6±31.5 °C

PluriSln 1

PluriSln 1 is an inhibitor of stearoyl-coA desaturase (SCD), and is a pluripotent cell-specific inhibitor.

  • CAS Number: 91396-88-2
  • MF: C12H11N3O
  • MW: 213.235
  • Catalog: Stearoyl-CoA Desaturase (SCD)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 335.7±15.0 °C at 760 mmHg
  • Melting Point: 177-178℃
  • Flash Point: 156.9±20.4 °C

diclofenamide

Dichlorphenamide(Diclofenamide) is a carbonic anhydrase inhibitor that is used in the treatment of glaucoma. Target: Carbonic AnhydraseDichlorphenamide is a sulfonamide and a carbonic anhydrase inhibitor of the meta-Disulfamoylbenzene class. This drug has the same side-effects as acetazolamide, for which it is a useful substitute, except for a lesser tendency to cause dermatitis, renal calculi and metabolic acidosis. It may induce a more pronounced renal loss of potassium [1]. An average daily dose of 33 mg of diclofenamide, a carbonic-anhydrase inhibitor, was added to the anti-epileptic medication already employed in 105 cases of severe epilepsy which had shown insufficient clinical improvement. A favourable action on seizures, often accompanied by an improvement in the EEG tracing, was observed in 83 cases. The effect was of long duration in 47 cases in that it lasted for more than a year. It persisted for one to twelve months in a further 17 cases, while in 19 patients, who had reacted favourably to the treatment, medication had to be suspended because of intolerance [2].

  • CAS Number: 120-97-8
  • MF: C6H6Cl2N2O4S2
  • MW: 305.159
  • Catalog: Carbonic Anhydrase
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 590.5±60.0 °C at 760 mmHg
  • Melting Point: 239-241ºC
  • Flash Point: 310.9±32.9 °C

MK-8617

MK-8617 is an orally active pan-inhibitor of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) with an IC50 of 1 nM for PHD2.

  • CAS Number: 1187990-87-9
  • MF: C24H21N5O4
  • MW: 443.45500
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(+)-Ketoconazole

(+)-Ketoconazole is an imidazole anti-fungal agent, a CYP3A4 inhibitor.Target: CYP3A4 (+)-Ketoconazole, an imidazole anti-fungal agent, has often produced features of androgen deficiency including decreased libido, gynecomastia, impotence, oligospermia, and decreased testosterone levels, in men being treated for chronic mycotic infections [1]. (+)-Ketoconazole also is a cytochrome P450 inhibitor [2].(+)-Ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver [3].Clinical indications: Candida infection; Dermatophytosis; Folliculitis FDA Approved Date: Toxicity: teratogenesis; liver injuries; adrenal gland problems

  • CAS Number: 142128-59-4
  • MF: C26H28Cl2N4O4
  • MW: 531.43
  • Catalog: Fungal
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KKII5

KKII5 is a potent Lipoxygenase (LOX-1) inhibitor with an IC50 of 19 μM. KKII5 inhibits lipid peroxidation[1].

  • CAS Number: 6381-55-1
  • MF: C16H14N2S
  • MW: 266.36
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 181-183ºC
  • Flash Point: N/A

Lovastatin

Lovastatin is a cell-permeable HMG-CoA reductase inhibitor used to lower cholesterol.

  • CAS Number: 75330-75-5
  • MF: C24H36O5
  • MW: 404.540
  • Catalog: Ferroptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 559.2±50.0 °C at 760 mmHg
  • Melting Point: 175°C
  • Flash Point: 185.3±23.6 °C

VTP-27999 (Hydrochloride)

VTP-27999 Hcl is an alkyl amine Renin inhibitor; VTP-27999 is useful for Hypertension and End-Organ Diseases.IC50 value:Target: Renin

  • CAS Number: 1264191-73-2
  • MF: C26H42Cl2N4O5
  • MW: 561.54100
  • Catalog: Renin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L 669262

L-669,262, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, with an IC50 of 0.10 ng/mL for rat liver HMG-CoA[1].

  • CAS Number: 130468-11-0
  • MF: C25H36O6
  • MW: 432.55
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.16g/cm3
  • Boiling Point: 609.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 202.1ºC

SPL 334

SPL-334 is a potent and selective S-Nitrosoglutathione reductase (GSNOR) inhibitor. SPL-334 causes a significant reduction in the production of Th2 cytokines IL-5 and IL-13 and the levels of the chemokine CCL11 (eotaxin-1) in the airways. SPL-334 can be used in research of allergic airway inflammation[1].

  • CAS Number: 688347-51-5
  • MF: C22H15N3O3S2
  • MW: 433.503
  • Catalog: GSNOR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 694.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 373.5±34.3 °C

Enoximone

Enoximone is an inotropic vasodilating agent and a selective and orally active phosphodiesterase III (PDE3) inhibitor with an IC50 of 5.9 μM. Enoximone induces vasodilatation and increases intracellular levels of cAMP by inhibiting cGMP-inhibited PDE. Enoximone also exhibits PDE4 inhibitory effect with an IC50 of 21.1 μM for myocardial PDE4A. Enoximone has the potential for congestive heart failure research and has bronchodilatory, antiasthma and anti-inflammatory effects[1][2][3].

  • CAS Number: 77671-31-9
  • MF: C12H12N2O2S
  • MW: 248.301
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 255-258°C
  • Flash Point: N/A

17-AAG

17-AAG is a potent HSP90 inhibitor with an IC50 of 5 nM, having a 100-fold higher binding affinity for tumour cell derived HSP90 than normal cell derived HSP90.

  • CAS Number: 75747-14-7
  • MF: C31H43N3O8
  • MW: 585.688
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 797.8±60.0 °C at 760 mmHg
  • Melting Point: 201-203ºC
  • Flash Point: 436.3±32.9 °C

hCAII-IN-1

hCAII-IN-1 (compound 7f) is a potent and selective inhibitor of carbonic anhydrase (CA II/IX) with Kis of 1.2 and 113.6 nM, respectively. hCAII-IN-1 has the potential for the research of cancer diseases[1].

  • CAS Number: 1807520-24-6
  • MF: C21H21BrN6O4S
  • MW: 533.40
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Epiursolic Acid

3-Epiursolic Acid is a triterpenoid isolated from Myrtaceae, acts as a competitive inhibitor of cathepsin L (ICIC50, 6.5 μM; Ki, 19.5 μM), with no obvious effect on cathepsin B[1].

  • CAS Number: 989-30-0
  • MF: C30H48O3
  • MW: 456.700
  • Catalog: Cathepsin
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 556.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 304.7±26.6 °C

WYC-209

WYC-209, a synthetic retinoid, inhibits proliferation of malignant murine melanoma tumor-repopulating cells (TRCs) with an IC50 of 0.19 μM, has long-term effects and little toxicity, and induces TRCs apoptosis primarily via the caspase 3 pathway. The primary cellular target of WYC-209 is retinoic acid receptor (RAR)[1].

  • CAS Number: 2131803-90-0
  • MF: C20H20N2O3S
  • MW: 368.45
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bexarotene-d3

Bexarotene-d3 (LGD1069-d3) is the deuterium labeled Bexarotene. Bexarotene (LGD1069) is a high-affinity and selective retinoid X receptors (RXR) agonist with EC50s of 33, 24, 25 nM for RXRα, RXRβ, and RXRγ, respectively. Bexarotene shows limited affinity for RAR receptors (EC50 >10000 nM). Bexarotene can be used for the research of cutaneous T-cell lymphoma[1][2][3][4].

  • CAS Number: 166175-35-5
  • MF: C24H25D3O2
  • MW: 351.50
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RTS-V5

RTS-V5 is a dual HDAC/proteasome inhibitor with IC50s of 6.9, 18, 15, 0.27, 0.53 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, respectively.

  • CAS Number: 2285346-31-6
  • MF: C27H35N5O6
  • MW: 525.60
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2183240

LY2183240 is a novel and highly potent blocker of anandamide uptake (IC50 = 270 pM). LY2183240 inhibits fatty acid amide hydrolase (FAAH) activity (IC50 = 12.4 nM). IC50: 270 pM (anandamide uptake); 12.4 nM (FAAH)Target: FAAH; Anandamide uptakeFollowing i.p. administration in rats, LY2183240 increases brain anandamide concentration and exerts antinociceptive effects in formalin model of pain.

  • CAS Number: 874902-19-9
  • MF: C17H17N5O
  • MW: 307.350
  • Catalog: FAAH
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 506.1±53.0 °C at 760 mmHg
  • Melting Point: 87-88ºC
  • Flash Point: 259.9±30.9 °C

Isovalerylcarnitine-d9 chloride

Isovalerylcarnitine-d9 (chloride) is the deuterium labeled Isovalerylcarnitine (chloride)[1]. Isovalerylcarnitine chloride, a product of the catabolism of L-leucine, is a potent activator of the Ca2+-dependent proteinase (calpain) of human neutrophils[2].

  • CAS Number: 1334532-23-8
  • MF: C12H15D9ClNO4
  • MW: 290.83
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A