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-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

PSI-6130

PSI-6130 is a potent and selective inhibitor of HCV NS5B polymerase, and inhibits HCV replication with a mean IC50 of 0.6 μM. 

  • CAS Number: 817204-33-4
  • MF: C10H14FN3O4
  • MW: 259.234
  • Catalog: HCV
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 482.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 245.5±31.5 °C

1H-Tetrazole-5-carboxamide, N-(5-(3-(4-acetyl-3-hydroxy-2-propylphenox y)propoxy)-4-chloro-2-methylphenyl)-, monosodium salt

CGP-35949 sodium is a LTD4 antagonist with phospholipase inhibitory activity. CGP-35949 sodium can be used for research of asthma[1].

  • CAS Number: 111130-13-3
  • MF: C23H25ClN5NaO5
  • MW: 509.92
  • Catalog: Leukotriene Receptor
  • Density: N/A
  • Boiling Point: 597.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 315ºC

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

Patamostat

Patamostat (E-3123) is a potent protease inhibitor. Patamostat potently inhibits trypsin, plasmin and thrombin with IC50s of 39 nM, 950 nM and 1.9 μM, respectively. E-3123 may possess suppressing effects on pathogenesis and development of acute pancreatitis[1][2].

  • CAS Number: 114568-26-2
  • MF: C20H20N4O4S
  • MW: 412.46200
  • Catalog: Ser/Thr Protease
  • Density: 1.41g/cm3
  • Boiling Point: 701.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 378.1ºC

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

PCSK9-IN-13

PCSK9-IN-13(compound 3f) is a potent PCSK9 inhibitor, which can antagonize low-density lipoprotein (LDL) receptor binding by binding to PCSK9, with an IC50 of 537 nM[1].

  • CAS Number: 2244129-23-3
  • MF: C30H33N5O2
  • MW: 495.62
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Betrixaban hydrochloride

Betrixaban (PRT054021) hydrochloride is a highly potent, selective, and orally efficacious factor Xa (fXa) inhibitor with an IC50 of 1.5 nM. Betrixaban hydrochloride shows antithrombotic effect[1][3].

  • CAS Number: 2099719-47-6
  • MF: C23H23Cl2N5O3
  • MW: 488.37
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cbl-b-IN-13

Cbl-b-IN-13 (Example 520) is a Cbl-b inhibitor with an IC50 of <100 nM. Cbl-b-IN-13 has the ability to activate T-cells[1].

  • CAS Number: 2368841-85-2
  • MF: C29H30F3N5O2
  • MW: 537.58
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RXPA 380

RXPA 380 is a C-terminal specific angiotensin-converting enzyme (ACE) inhibitor with a Ki of 3 nM. RXPA 380 inhibits C-domain mutants of human recombinant ACE with an IC50 of 2.5 nM[1].

  • CAS Number: 564479-79-4
  • MF: C33H36N3O7P
  • MW: 617.63
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Perindopril-d4 erbumine

Perindopril-d4 t-butylamine salt is the deuterium labeled Perindopril t-butylamine salt. Perindopril t-butylamine salt is a long-acting ACE inhibitor of which is used to treat high blood pressure, heart failure or stable coronary artery disease[1][2].

  • CAS Number: 1356929-59-3
  • MF: C23H39D4N3O5
  • MW: 445.62900
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

K777

K777 is a potent, orally active and irreversible cysteine protease inhibitor. K777 is also a potent CYP3A4 inhibitor with an IC50 of 60 nM and a selective CCR4 antagonist featuring the potent chemotaxis inhibition. K777 irreversibly inhibits Cruzain, the major cysteine protease of Trypansoma cruzi, and cathepsins B and L. K777 is a broad-spectrum antiviral by targeting cathepsin-mediated cell entry. K777 inhibits SARS-CoV and EBOV pseudovirus entry with IC50 values of 0.68 nM and 0.87 nM, respectively[1][2][3].

  • CAS Number: 233277-99-1
  • MF: C32H38N4O4S
  • MW: 574.73
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3',4',7,8-Tetrahydroxyflavone

7,8,3′,4′-Tetrahydroxyflavone (compound 2) is a potent xanthine oxidase (XOD) inhibitor with an IC50 value of 10.488 µM[1].

  • CAS Number: 3440-24-2
  • MF: C15H10O6
  • MW: 286.24
  • Catalog: Xanthine Oxidase
  • Density: 1.654g/cm3
  • Boiling Point: 618.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 240.6ºC

SB-435495 ditartrate

SB-435495 ditartrate is a potent, selective, reversible, non-covalent and orally active Lp-PLA2 inhibitor with an IC50 of 0.06 nM[1][3].

  • CAS Number: 304694-43-7
  • MF: C46H52F4N6O14S
  • MW: 1021.00
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Abiraterone

Abiraterone is a potent, selective, and irreversible CYP17 inhibitor with IC50 of 2 to 4 nM.

  • CAS Number: 154229-19-3
  • MF: C24H31NO
  • MW: 349.509
  • Catalog: Cytochrome P450
  • Density: 1.14g/cm3
  • Boiling Point: 500.2±50.0 °C at 760 mmHg
  • Melting Point: 227-228 °C
  • Flash Point: 256.3±30.1 °C

HaloPROTAC-E

HaloPROTAC-E is a novel HaloPROTAC potent degrader, inducing reversible degradation of two endosomally localized proteins, SGK3 and VPS34, with a DC50 of 3-10 nM, remarkably selective inducing only degradation of the Halo tagged endogenous VPS34 complex (VPS34, VPS15, Beclin1, and ATG14).

  • CAS Number: 2365478-58-4
  • MF: C39H56ClN5O8S
  • MW: 790.41
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Verucopeptin

Verucopeptin is a potent HIF-1 (IC50=0.22 μM) inhibitor and decreases the expression of HIF-1 target genes and HIF-1α protein levels[1][2]. Verucopeptin strongly inhibits v-ATPase activity by directly targeting the v-ATPase ATP6V1G subunit but not ATP1V1B2 or ATP6V1D. Verucopeptin exhibits antitumor activity against multidrug resistance (MDR) cancers and can be used for cancer research[3].

  • CAS Number: 138067-14-8
  • MF: C43H73N7O13
  • MW: 896.07900
  • Catalog: Proton Pump
  • Density: 1.27g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Integracin B

Integracin B is a potent dimeric alkyl aromatic inhibitor of HIV-1 integrase discovered from the screening of fungal extracts using an in vitro assay. Integracin B inhibits both coupled and strand transfer activity of HIV-1 integrase[1].

  • CAS Number: 224186-05-4
  • MF: C35H54O7
  • MW: 586.79900
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LONAFARNIB

(Rac)-Lonafarnib (Sch66336 racemate) is the racemate of Lonafarnib. Lonafarnib is a potent and orally active farnesyl transferase (FTase) inhibitor. Lonafarnib inhibits the activities of H-ras, K-ras and N-ras with IC50 values of 1.9 nM, 5.2 nM and 2.8 nM, respectively. Lonafarnib also has anti-hepatitis delta virus (HDV) activities[1].

  • CAS Number: 193275-86-4
  • MF: C27H31Br2ClN4O2
  • MW: 638.822
  • Catalog: Farnesyl Transferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 710.4±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 383.5±35.7 °C

Tilpisertib fosmecarbil

Tilpisertib fosmecarbil is a potent serine/threonine kinase inhibitor. Tilpisertib fosmecarbil has anti-inflammatory activity[1].

  • CAS Number: 2567459-64-5
  • MF: C35H36ClN8O7P
  • MW: 747.14
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NDI-091143

NDI-091143 is a novel ATP-citrate lyase inhibitor.

  • CAS Number: 2375840-87-0
  • MF: C20H14ClF2NO5S
  • MW: 453.84
  • Catalog: ATP Citrate Lyase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Desirudin

Desirudin (CGP 39393) is a thrombin inhibitor. Desirudin can inhibit the formation of blood clots and venous stasis thrombosis, which is used for the research of thrombocytopenia or platelet dysfunction[1][2].

  • CAS Number: 120993-53-5
  • MF: C287H440N80O110S6
  • MW:
  • Catalog: Thrombin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ganoderic acid B

Ganoderic acid B is a triterpene isolated from a mushroom Ganoderma lucidum. Ganoderic acid B inhibits the activation of Epstein-Barr virus (EBV) antigens as telomerase inhibitor. Ganoderic acid B is a moderately active inhibitor against HIV-1 protease[1][2][3].

  • CAS Number: 81907-61-1
  • MF: C30H44O7
  • MW: 516.666
  • Catalog: HIV Protease
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 689.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.4±28.0 °C

Ciluprevir

Ciluprevir(BILN 2061) is a specific and potent peptidomimetic inhibitor of the HCV NS3 protease with an IC50 of 3.0 nM.

  • CAS Number: 300832-84-2
  • MF: C40H50N6O8S
  • MW: 774.93
  • Catalog: HCV
  • Density: 1.4±0.0 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JZP-MA-11

JZP-MA-11 is a positron emission tomography (PET) ligand targeting the endocannabinoid α/β-hydrolase domain 6 (ABHD6) enzyme. JZP-MA-11 selectively inhibits ABHD6 with an IC50 value of 126 nM. JZP-MA-11 can cross the blood-brain barrier (BBB). [18F]JZP-MA-11 has the potential for preclinical evaluation targeting the brain ABHD6 in mice and nonhuman primate (NHP)[1].

  • CAS Number: 1672691-50-7
  • MF: C15H17FN4O2S
  • MW: 336.38
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Guggulsterone E&Z

Guggulsterone is a plant sterol derived from the gum resin of the tree Commiphora wightii. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases and JNK, inhibition of Akt[1]. Guggulsterone, a farnesoid X receptor (FXR) antagonist, decreases CDCA-induced FXR activation with IC50s of 17 and 15 μM for Z- and E-Guggulsterone, respectively[2].

  • CAS Number: 95975-55-6
  • MF: C21H28O2
  • MW: 312.446
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 463.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.3±25.7 °C

N[2-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl]quinoline-3-carboxamide Hydrochloride

BML-280 (VU0285655-1) is a potent and selective phospholipase D2 (PLD2) inhibitor. BML-280 has the ability to prevent caspase-3 cleavage and reduction in cell viability induced by high glucose. BML-280 can be used for rheumatoid arthritis research[1][2].

  • CAS Number: 1158347-73-9
  • MF: C25H27N5O2
  • MW: 429.51400
  • Catalog: Interleukin Related
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A