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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3,4-Dimethoxyphenol

3,4-Dimethoxyphenol is a plant-derived phenylpropanoid compound and can use as a whitening agent in cosmetics. 3,4-Dimethoxyphenol has tyrosinase-inhibiting activity[1]. 3,4-Dimethoxyphenol has potent antioxidant effect isolated from the bacterial fermentation broth[2].

  • CAS Number: 2033-89-8
  • MF: C8H10O3
  • MW: 154.163
  • Catalog: Tyrosinase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 271.2±20.0 °C at 760 mmHg
  • Melting Point: 79-82 °C(lit.)
  • Flash Point: 117.8±21.8 °C

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

JTK-109

JTK-109 is an inhibitor of hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitor and inhibits G1b and G3a subgenomic replicons and recombinant enzymes.

  • CAS Number: 480462-62-2
  • MF: C37H33ClFN3O4
  • MW: 638.13
  • Catalog: HCV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC697923

NSC697923 is a potent UBE2N (ubiquitin-conjugating enzyme E2 N, Ubc13) inhibitor. NSC697923 induces neuroblastoma (NB) cell death via promoting nuclear importation of p53 in p53 wild-type NB cells. NSC697923 also induces cell death in p53 mutant NB cells by activation of JNK-mediated apoptotic pathway. NSC697923 inhibits DNA damage and NF-κB signaling. Antitumor activity[1][2].

  • CAS Number: 343351-67-7
  • MF: C11H9NO5S
  • MW: 267.25800
  • Catalog: Apoptosis
  • 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

DPP-4-IN-2

DPP-4-IN-2 (compound b2) is a potent DPP-4 (dipeptidyl peptidase 4) inhibitor, with an IC50of 79 nM. DPP-4-IN-2 is a structurally analogs of Alogliptin (HY-A0023A). DPP-4-IN-2 can be used for diabetes research[1].

  • CAS Number: 2133900-95-3
  • MF: C18H18N6O
  • MW: 334.38
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Suc-Gly-Gly-Phe-pNA

Suc-Gly-Gly-Phe-pNA is the chymotrypsin substrate with an Km value of 1.6 mM[1][2].

  • CAS Number: 68982-90-1
  • MF: C23H25N5O8
  • MW: 499.47300
  • Catalog: Proteasome
  • Density: 1.401g/cm3
  • Boiling Point: 1005.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 562ºC

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

DPC-681

DPC-681 is a potent and selective inhibitor of HIV protease with IC90s for wild-type HIV-1 of 4 to 40 nM.IC50 value: 4 - 40 nM [1]Target: HIV proteasein vitro: DPC 681 is extremely potent inhibitor of wild-type HIV-1. When all of the HIV-1 strains tested are considered, the average concentrations required for 90% inhibition of replication were 7.3 ± 3.4 for DPC 681. DPC 681 shows no loss in potency toward recombinant mutant HIVs with the D30N mutation and a fivefold or smaller loss in potency toward mutant variants with three to five amino acid substitutions. [1]in vivo: The total body clearance (CL) of DPC 681 in dogs was high (1.8 liter/h/kg) equaling hepatic blood flow for this species (1.8 liter/h/kg). After an oral dosing, the Cmax increased ninefold between the 10- and 30-mg/kg DPC 681 dose groups. Bioavailability also increased between the 10- and 30-mg/kg dose groups (18.3 and 78.1%, respectively). These data suggest that hepatic extraction (first-pass effect) can be saturated in the dog. [1]

  • CAS Number: 284661-68-3
  • MF: C35H48FN5O5S
  • MW: 669.85
  • Catalog: HIV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

FTase Inhibitor I

Ftase inhibitor I (B581) is a potent, selective and peptidomimetic farnesyl transferase (FTase) inhibitor. Ftase inhibitor I shows selectivity for FTase over geranylgeranyl isoprenoid (Ras-GG) or the fatty acid myristate (Myr-Ras)[1].

  • CAS Number: 149759-96-6
  • MF: C22H38N4O3S2
  • MW: 470.69
  • Catalog: Farnesyl Transferase
  • Density: 1.161g/cm3
  • Boiling Point: 716.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 386.9ºC

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

Ono 3403

Ono 3403 is a synthetic serine protease inhibitor. Ono 3403 inhibits lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production. ONO-3403 also has an antitumor effect on malignant tumors.

  • CAS Number: 181586-07-2
  • MF: C26H31N3O8S
  • MW: 545.6
  • Catalog: Apoptosis
  • 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

JP104

JP104, a aryl carbamate, is an irreversible FAAH inhibitor with a pIC50 of ~8[1].

  • CAS Number: 887264-45-1
  • MF: C25H34N2O3
  • MW: 410.549
  • Catalog: FAAH
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 565.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 296.0±30.1 °C

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

Ilexsaponin B2

Ilexsaponin B2 is a saponin isolated from the root of Ilex pubescens Hook. et Arn. Ilexsaponin B2 is a potent phosphodiesterase 5 (PDE5) and PDEI inhibitor with IC50 values of 48.8 μM and 477.5 μM, respectively[1].

  • CAS Number: 108906-69-0
  • MF: C47H76O17
  • MW: 913.09600
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

UK 356618

UK 356618 (Compound 4j) is a potent and selective inhibitor of matrix metalloprotease-3 (MMP-3) with an IC50 of 5.9 nM. UK 356618 is >140-fold less potent against MMP-1 (IC50 of 51,000 nM), MMP-2 (IC50 of 1790 nM), MMP-9 (IC50 of 840 nM) and MMP-14 (IC50 of 1900 nM) compared with MMP-3[1].

  • CAS Number: 230961-08-7
  • MF: C34H43N3O4
  • MW: 557.72300
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Coptisine chloride

Coptisine chloride is an alkaloid from Chinese goldthread, and acts as an efficient uncompetitive IDO inhibitor with a Ki value of 5.8 μM and an IC50 value of 6.3 μM.

  • CAS Number: 6020-18-4
  • MF: C19H14ClNO4
  • MW: 355.772
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: 1.51g/cm3
  • Boiling Point: 601.5ºC at 760 mmHg
  • Melting Point: >258ºC (dec.)
  • Flash Point: 190.4ºC

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

Propentofylline

Propentofylline is a xanthine-derivative that inhibits adenosine uptake and blocks phosphodiesterase activity. Propentofylline has neuroprotective, antiproliferative, and anti-inflammatory effects that improve cognition and dementia severity in patients with Alzheimer's disease or vascular dementia.

  • CAS Number: 55242-55-2
  • MF: C15H22N4O3
  • MW: 306.360
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 541.4±56.0 °C at 760 mmHg
  • Melting Point: 64-66ºC
  • Flash Point: 281.2±31.8 °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

hCA I-IN-1

hCA I-IN-1 (Compound 6q) is a human carbonic anhydrase I (hCA I) inhibitor with Ki values of 38.3, 716.4, 940.1 and 192.8 nM against hCA I, hCA II, hCAIX and hCAXII, respectively[1].

  • CAS Number: 2417232-26-7
  • MF: C27H23N5O4S
  • MW: 513.57
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nelfinavir mesylate

Nelfinavir(AG-1341) is a potent and orally bioavailable human immunodeficiency virus HIV-1 protease inhibitor (Ki=2 nM) and is widely prescribed in combination with HIV reverse transcriptase inhibitors for the treatment of HIV infection. IC50 Valur: 2 nM (Ki for HIV-1 protease) [2]Target: HIV Proteasein vitro: In vitro exposure (72 hours) of HAECs to NEL (0.25-2 μg/mL) decreased both basal (2.5-fold) and insulin-induced NO production (4- to 5-fold). NEL suppressed insulin-induced phosphorylation of both Akt and eNOS at serine residues 473 and 1177, respectively. NEL decreased tyrosine phosphorylation of IR-β, IRS-1, and PI3K. Coexposure to troglitazone (TRO; 250 nM) ameliorated the suppressive effects of NEL on insulin signaling and NO production. Coexposure to TRO also increased eNOS expression in NEL-treated HAECs [1]. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively [2].in vivo: In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans [2].

  • CAS Number: 159989-65-8
  • MF: C33H49N3O7S2
  • MW: 663.888
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: 786.8ºC at 760 mmHg
  • Melting Point: 131-135ºC
  • Flash Point: 429.7ºC