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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FASN-IN-3

FASN inhibitor 1 is a fatty acid synthase (FASN) inhibitor extracted from patent US20170119786A1, compound 242A.

  • CAS Number: 2097262-60-5
  • MF: C24H24N4O
  • MW: 384.4798
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ABT-100

ABT-100 is a potent, highly selective and orally active farnesyltransferase inhibitor. ABT-100 inhibits cell proliferation (IC50s of 2.2 nM, 3.8 nM, 5.9 nM, 6.9 nM, 9.2 nM, 70 nM and 818 nM for EJ-1, DLD-1, MDA-MB-231, HCT-116, MiaPaCa-2, PC-3, and DU-145 cells, respectively), increases apoptosis and decreases angiogenesis. ABT-100 possesses broad-spectrum antitumor activity[1].

  • CAS Number: 450839-40-4
  • MF: C27H19F3N4O3
  • MW: 504.46000
  • Catalog: Farnesyl Transferase
  • Density: 1.29g/cm3
  • Boiling Point: 722ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 390.5ºC

Iristectorigenin B

Iristectorigenin B (Iristectrigenin B) is a liver X receptor (LXR) modulator. Iristectrigenin B stimulates the transcriptional activity of both LXR-α and LXR-β[1].

  • CAS Number: 86849-77-6
  • MF: C17H14O7
  • MW: 330.28900
  • Catalog: LXR
  • Density: 1.483g/cm3
  • Boiling Point: 621.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 232.8ºC

2-Deoxy-D-glucose-13C

2-Deoxy-D-glucose-13C is the 13C labeled 2-Deoxy-D-glucose. 2-Deoxy-D-glucose is a glucose analog that acts as a competitive inhibitor of glucose metabolism, inhibiting glycolysis via its actions on hexokinase[1][2].

  • CAS Number: 201612-55-7
  • MF: C6H12O5
  • MW: 165.14900
  • Catalog: HSV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

hCAIX/XII-IN-3

hCAIX/XII-IN-3 (compound 6q) is a potent and selective hCAIX and hCAXIIinhibitor with Ki values of >10000, >10000, 66.2, 4.4 nM for hCAI, hCAII, hCAIX and hCAXII, respectively[1].

  • CAS Number: 2414629-94-8
  • MF: C20H13F3N2O4
  • MW: 402.32
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC-87877 disodium

NSC-87877 disodium is a potent inhibitor of Shp2 and Shp1 protein tyrosine phosphatases (SH-PTP2 and SH-PTP1), with IC50 values of 0.318 μM, 0.355 μM shp2 and shp1, respectively[1]. NSC-87877 also inhibits dual-specificity phosphatase 26 (DUSP26)[2].

  • CAS Number: 56932-43-5
  • MF: C19H11N3Na2O7S2
  • MW: 503.41600
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Apararenone

Apararenone (MT-3995) is a novel non-steroidal mineralocorticoid receptor antagonists under development for the treatment of diabetic nephropathies and non-alcoholic steatohepatitis.

  • CAS Number: 945966-46-1
  • MF: C17H17FN2O4S
  • MW: 364.391
  • Catalog: Mineralocorticoid Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 594.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 313.2±32.9 °C

Fuzapladib sodium

Fuzapladib sodium (IS-741 sodium) is a potent and orally active phospholipase A2 inhibitor. Fuzapladib sodium can block the adhesion of inflammatory cells to microvascular endothelial cells, inhibits the infiltration of neutrophils into the pancreas or acute pancreatitis, and has anti-acute pancreatitis effects[1][2].

  • CAS Number: 141284-73-3
  • MF: C15H19F3N3NaO3S
  • MW: 401.38000
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: 522.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 270.1ºC

ALP/Carbonic anhydrase-IN-1

ALP/Carbonic anhydrase-IN-1 (Compound 1e) is a dual carbonic anhydrase (CA) and alkaline phosphatase (ALP) inhibitor. ALP/Carbonic anhydrase-IN-1 shows IC50 values of 0.44 µM, 1.61 µM, 0.51 µM, and 0.107 µM for CA-II, CA-IX, CA-XII, and ALP, respectively[1].

  • CAS Number: 2091887-74-8
  • MF: C15H16N2
  • MW: 224.30
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydromethysticin

Dihydromethysticin is one of the six major kavalactones found in the kava plant; has marked activity on the induction of CYP3A23.

  • CAS Number: 19902-91-1
  • MF: C15H16O5
  • MW: 276.284
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 476.1±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 214.1±28.8 °C

SAR127303

SAR127303 is an effective covalent inhibitor of MAGL. SAR127303 behaves as a selective and competitive inhibitor of mouse and human MAGL.

  • CAS Number: 1352011-38-1
  • MF: C16H17ClF6N2O4S
  • MW: 482.83
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D-Thr-OH

D-Tyrosine is the D-isomer of tyrosine. D-Tyrosine negatively regulates melanin synthesis by inhibiting tyrosinase activity. D-Tyrosine inhibits biofilm formation and trigger the self-dispersal of biofilms without suppressing bacterial growth[1][2].

  • CAS Number: 556-02-5
  • MF: C9H11NO3
  • MW: 181.189
  • Catalog: Tyrosinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 385.2±32.0 °C at 760 mmHg
  • Melting Point: 310-314ºC
  • Flash Point: 186.7±25.1 °C

Indeno[1,2-b]furazano[3,4-E]pyrazin-9-one

SMER3, a Rapamycin enhancer, is a selective Skp1-Cullin-F-box (SCF)Met30 ubiquitin ligase inhibitor. SMER3 enhances Rapamycin's growth inhibitory effect by inhibition of SCFMet30[1].

  • CAS Number: 67200-34-4
  • MF: C11H4N4O2
  • MW: 224.175
  • Catalog: E1/E2/E3 Enzyme
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 437.2±55.0 °C at 760 mmHg
  • Melting Point: 296 °C(dec.)
  • Flash Point: 218.2±31.5 °C

ent-Tadalafil

ent-Tadalafil (ent-IC-351), compound (6S,12aS), is a inactive cis-enantiomer of compound (6R,12aS). compound (6R,12aS) is a potent PDE5 inhibitor with an IC50 of 0.090 μM, while ent-Tadalafil is inactive at concentrations up to 10 µM[1].

  • CAS Number: 629652-72-8
  • MF: C22H19N3O4
  • MW: 389.40400
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.51±0.1 g/cm3 (20 ºC 760 Torr)
  • Boiling Point: N/A
  • Melting Point: 302-304 ºC
  • Flash Point: N/A

MK-5172 (potassium salt)

Grazoprevir potassium salt (MK-5172 potassium salt) is a selective inhibitor of Hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants, with Kis of 0.01 nM (gt1b), 0.01 nM (gt1a), 0.08 nM (gt2a), 0.15 nM (gt2b), 0.90 nM (gt3a), respectively.

  • CAS Number: 1206524-86-8
  • MF: C38H49KN6O9S
  • MW: 804.994
  • Catalog: HCV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GP3269

GP3269 is a potent, selective, and orally active inhibitor of human adenosine kinase (AK) with an IC50 of 11 nM. GP3269 exhibits anticonvulsant activity in rats[1].

  • CAS Number: 186393-42-0
  • MF: C23H21FN4O3
  • MW: 420.44
  • Catalog: Adenosine Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acitretin (sodium)

Acitretin sodium(Ro 10-1670) is a second-generation, systemic retinoid that has been used in the treatment of psoriasis.Target: RAR/RXRAcitretin sodium is a second-generation, systemic retinoid that has been approved for the treatment of psoriasis since 1997. It can be considered one of the treatments of choice for pustular and erythrodermic psoriasis. However, the efficacy of acitretin sodium as a monotherapy for plaque psoriasis is less, although it is often used in combination therapy with other systemic psoriasis therapies, especially ultraviolet B or psoralen plus ultraviolet A phototherapy, to increase efficacy. Such combination treatments may potentially minimise toxicity by using lower doses of each of the two agent [1].Thirty-nine male adult Wistar albino rats were divided into 3 groups as two experimental groups and one control group. The first group consisting 14 rats were applied orally standard dose (0.75 mg/kg/day) acitretin sodium and the second group consisting 16 rats were applied high dose (1.5 mg/kg/day) acitretin sodium. Acitretin sodium was given within dimetil sulphoxide (DMSO), which was diluted with saline solution as a ratio of 1/10, in order to increase its solubility. The control group consisting 9 rats were given only saline solution including DMSO for 8 weeks. After 8 weeks of the administration, half of the rats in the first and second groups and the entire control group were sacrificed under deep ether anaesthesia and bilateral orchiectomy was made. The remainingrats were compared with the control group using a similar method at the end of 8 weeks of wash-off period. The orchiectomy materials were histopathologically evaluated under the light microscope for spermatogenesis according to parameters including spermatogenetic activity, spermatogenetic organization, seminiferous tubular diameter, interstitial Leydig cells and fibroblasts. In our study it was concluded that the standard and high doses of acitretin sodium do not have any effect on the spermatogenesis of threats [2].Clinical indications: PsoriasisFDA Approved Date: Toxicity: nausea; headache; itching; red or flaky skin; dry or red eyes; dry mouth; depression; hair loss

  • CAS Number: 925701-88-8
  • MF: C21H25NaO3
  • MW: 348.41
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML148

ML148 is a potent and selective 15-PGDH inhibitor with an IC50 of 56 nM. ML148 has the potential for the research of prostaglandin-signaling pathways[1].

  • CAS Number: 451496-96-1
  • MF: C20H21N3O
  • MW: 319.40
  • Catalog: 15-PGDH
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 543.4±52.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 282.5±30.7 °C

3α-Hydroxy pravastatin sodium

3α-Hydroxy pravastatin sodium is the major metabolite of Pravastatin. Pravastatin is a competitive HMG-CoA reductase inhibitor[1][2].

  • CAS Number: 81093-43-8
  • MF: C23H35NaO7
  • MW: 446.51000
  • Catalog: HMG-CoA Reductase (HMGCR)
  • 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 and CYP24A1 inhibitor.Target: CYP3A4 CYP24A1Ketoconazole, 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] CYP24A1 inhibitor enhances antiproliferative effects, increases systemic calcitriol exposure, and promotes the activation of caspase-independent apoptosis pathway.[4]

  • CAS Number: 65277-42-1
  • MF: C26H28Cl2N4O4
  • MW: 531.431
  • Catalog: Fungal
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 753.4±60.0 °C at 760 mmHg
  • Melting Point: 146°C
  • Flash Point: 409.4±32.9 °C

GNE-6468

GNE-6468 is a potent and selective RORγ(RORc) agonists with an EC50 value of 13 nM for HEK-293 cell.

  • CAS Number: 1677668-27-7
  • MF: C23H16ClN3O4
  • MW: 433.84
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mergetpa

Mergetpa is a carboxypeptidase inhibitor used to block the conversion of kinins and B2 receptor antagonists to metabolites lacking the C-terminal arginine[1].

  • CAS Number: 77102-28-4
  • MF: C7H15N3O2S2
  • MW: 237.34
  • Catalog: Carboxypeptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP-640186 hydrochloride

CP-640186 hydrochloride is a potent and cell-permeable Acetyl-CoA carboxylase (ACC) inhibitor with IC50s of 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively.

  • CAS Number: 591778-70-0
  • MF: C30H36ClN3O3
  • MW: 522.078
  • Catalog: Acetyl-CoA Carboxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Atorvastatin lactone

Atorvastatin lactone is a prodrug form of atorvastatin. Atorvastatin is an orally active 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor[1].

  • CAS Number: 125995-03-1
  • MF: C33H33FN2O4
  • MW: 540.625
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 674.8±55.0 °C at 760 mmHg
  • Melting Point: 103-106ºC
  • Flash Point: 361.9±31.5 °C

MK-0674

MK-0674 is a potent, orally bioavailable and selective cathepsin K inhibitor, with an IC50 of 0.4 nM, shows 1156, 1465, 11857 and 243 fold selectivity over Cat B, Cat F, Cat L and Cat S. MK-0674 exhibits long half-lives in rats, rabbits and rhesus monkeys[1].

  • CAS Number: 887781-62-6
  • MF: C26H27F6N3O2
  • MW: 527.50200
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nampt activator-1

Nampt activator-1 (compound 1) is a potent Nicotinamide phosphoribosyltransferase (NAMPT) activator, with EC50 of 3.3-3.7 μM[1].

  • CAS Number: 701929-65-9
  • MF: C16H17N3O3
  • MW: 299.32
  • Catalog: Nampt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK2647544

GSK2647544 is an orally available, selective inhibitor of Lp-PLA2. Lipoprotein-associated phospholipase (Lp-PLA2) is a calcium-independent phospholipase A2 with proinflammatory activities that is primarily secreted by monocyte-derived macrophages[1].

  • CAS Number: 1380426-95-8
  • MF: C24H18ClF3N4O3
  • MW: 502.87
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Saterinone hydrochloride

Saterinone hydrochloride is a phosphodiesterase III (PDE III) inhibitor.

  • CAS Number: 102685-83-6
  • MF: C27H31ClN4O4
  • MW: 511.01
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HELSS

Bromoenol lactone ((6E)-Bromoenol lactone) is a suicide-based irreversible, selective, potent inhibitor of calcium-independent phospholipase A2 (iPLA2β) with an IC50 value of approximately 7 μM, which inhibits antigen-stimulated mast cell exocytosis without blocking Ca2+ influx[1][2].

  • CAS Number: 88070-98-8
  • MF: C16H13BrO2
  • MW: 317.177
  • Catalog: Phospholipase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 467.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 236.2±28.7 °C

CP-610431

CP-610431 is a reversible, ATP-uncompetitive, isozyme-nonselective acetyl-CoA carboxylase (ACC) inhibitor. CP-610431 inhibits ACC1 and ACC2 with IC50s of ~50 nM. CP-610431 can be used for the research of metabolic syndrome[1].

  • CAS Number: 591778-83-5
  • MF: C30H37N3O2
  • MW: 471.63
  • Catalog: Acetyl-CoA Carboxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A