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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Cephaeline Dihydrochloride

(-)-Cephaeline dihydrochloride is an enantiomer of Cephaeline dihydrochloride. Cephaeline dihydrochloride is a selective CYP2D6 inhibtor with IC50 of 121 μM.

  • CAS Number: 5853-29-2
  • MF: C28H40Cl2N2O4
  • MW: 539.53
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GLPG1690

GLPG1690 is a first-in-class autotaxin (ATX) inhibitor, with an IC50 of 131 nM and Ki of 15 nM.

  • CAS Number: 1628260-79-6
  • MF: C30H33FN8O2S
  • MW: 588.699
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-04457845

PF-04457845 is a highly efficacious and selective FAAH inhibitor with IC50 values is 7.2±0.63 nM and 7.4±0.62 nM for hFAAH and rFAAH, respectively.

  • CAS Number: 1020315-31-4
  • MF: C23H20F3N5O2
  • MW: 455.43200
  • Catalog: FAAH
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Leucosceptoside A

Leucosceptoside A is a phenylethanoid glycoside with anti-hyperglycemic and anti-hypertensive activities. Leucosceptoside A shows inhibitory activity against α-glucosidase and PKCα (IC50 of 19.0 μM)[1][2][3].

  • CAS Number: 83529-62-8
  • MF: C30H38O15
  • MW: 638.61400
  • Catalog: PKC
  • Density: 1.545g/cm3
  • Boiling Point: 884.547ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 283.993ºC

GSTO1-IN-1

GSTO1-IN-1 is a potent glutathione S-transferase omega 1 (GSTO1) inhibitor with an IC50 of 31 nM.

  • CAS Number: 568544-03-6
  • MF: C10H12Cl2N2O3S
  • MW: 311.185
  • Catalog: Gutathione S-transferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP13-IN-31f

MMP13-IN-31f is a highly potent, selective, orally bioavailable MMP-13 inhibitor with IC50 of 0.036 nM; exhibits 5,000-fold selectivity for MMP-13 over MMP-2, >1,500-fold selectivity over MMP-10, and >27,000-fold selectivity over MMP-1, 3, 7, 8, 9, 14, and TACE; prevents IL-1/OSM induced in vitro degradation of BNC (70.8% inhibition of cartilage degradation at 1 µM).

  • CAS Number: 935759-55-0
  • MF: C24H19FN6O4S
  • MW: 506.509
  • Catalog: MMP
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Apremilast

Apremilast is an orally available inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4) with an IC50 of 74 nM.

  • CAS Number: 608141-41-9
  • MF: C22H24N2O7S
  • MW: 460.500
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 741.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 402.1±32.9 °C

Rosuvastatin D3

Rosuvastatin D3 (ZD 4522 D3) is a deuterium labeled Rosuvastatin. Rosuvastatin (ZD 4522) is a competitive HMG-CoA reductase inhibitor with an IC50 of 11 nM[1]. Rosuvastatin potently blocks human ether-a-go-go related gene (hERG) current with an IC50 of 195 nM, delayed cardiac repolarization, and thereby prolonged action potential durations (APDs) and corrected QT interval (QTc) intervals[2].

  • CAS Number: 1133429-16-9
  • MF: C22H25D3FN3O6S
  • MW: 484.56
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Hydroxy-4-methoxybenzaldehyde

2-Hydroxy-4-methoxybenzaldehyde, a chemical compound and an isomer of Vanillin, could be used to synthesis Urolithin M7[1]. 2-hydroxy-4-methoxybenzaldehyde is a potent tyrosinase inhibitor from three East African medicinal plants, Mondia whitei, Rhus vulgaris Meikle, and Sclerocarya caffra Sond[2].

  • CAS Number: 673-22-3
  • MF: C8H8O3
  • MW: 152.15
  • Catalog: Tyrosinase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 271.5±20.0 °C at 760 mmHg
  • Melting Point: 41-43 °C(lit.)
  • Flash Point: 112.1±15.3 °C

WS-383 free base

WS-383 (WS383) is a highly potent, selective, and cellular active inhibitor of DCN1-UBC12 interaction with IC50 of 11 nM; inhibits Cul3/1 neddylation selectively over other cullins and also induces accumulation of p21, p27 and NRF2; exhibits cellular target engagement to DCN1 in MGC-803 cells, enhances the thermal stability of cellular DCN1 protein even at 1 uM

  • CAS Number: 2247543-65-1
  • MF: C18H20ClN9S2
  • MW: 461.991
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Molidustat

Molidustat (BAY 85-3934) is a novel inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) with mean IC50 values of 480 nM for PHD1, 280 nM for PHD2, and 450 nM for PHD3.

  • CAS Number: 1154028-82-6
  • MF: C13H14N8O2
  • MW: 314.303
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 589.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 310.2±32.9 °C

Gü2602

Gü2602 is a potent, reversible cathepsin K (CatK) inhibitor with a Ki of 0.013 nM for mature CatK (mCatK). Gü2602 suppresses the autocatalytic activation of the cathepsin K zymogen[1].

  • CAS Number: 1627094-88-5
  • MF: C16H22N4O3
  • MW: 318.37
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TP-10

TP-10 is a PDE10A inhibitor with IC50 of 0.8 nM.IC50 value: 0.8 nM [1]Target: PDE10ATP-10 has extremely potent PDE10A inhibitory activity and highselectivity against other PDEs, and be active in the mouse behavioral model for positive symptoms. TP-10 demonstrats good in vitro and in vivo activity, the intrinsic clearance (CLint) of these compounds in mouse liver microsomes (MLM) was extremely high in assay (CLint>1000 mL/min/kg). [1]

  • CAS Number: 898563-00-3
  • MF: C26H19F3N4O
  • MW: 460.45000
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Spiraprilat

Spiraprilat is a potent angiotensin-converting enzyme (ACE) inhibitor. Spiraprilat has ability to improve left ventricular (LV) function and metabolism in anesthetized open-chest dogs with acute ventricular failure (ALVF)[1].

  • CAS Number: 83602-05-5
  • MF: C20H26N2O5S2
  • MW: 438.56100
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI 1840

PI-1840 is a potent and selective inhibitor for chymotrypsin-like (CT-L) (IC50 value = 27 ± 0.14 nM) over trypsin-like and peptidylglutamyl peptide hydrolyzing (IC50 values >100 μM) activities of the proteasome. IC50 value: 27 nM(CT-L activities of the proteasome) [1]Target: CT-L inhibitorin vitro: PI-1840 is over 100-fold more selective for the constitutive proteasome over the immunoproteasome. Mass spectrometry and dialysis studies demonstrate that PI-1840 is a noncovalent and rapidly reversible CT-L inhibitor. In intact cancer cells, PI-1840 inhibits CT-L activity, induces the accumulation of proteasome substrates p27, Bax, and IκB-α, inhibits survival pathways and viability, and induces apoptosis. Furthermore, PI-1840 sensitizes human cancer cells to the mdm2/p53 disruptor, nutlin, and to the pan-Bcl-2 antagonist BH3-M6 [1].in vivo: PI-1840 but not bortezomib suppresses the growth in nude mice of human breast tumor xenografts [1].

  • CAS Number: 1401223-22-0
  • MF: C22H26N4O3
  • MW: 394.46700
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AChE/hCA I/II-IN-1

AChE/hCA I/II-IN-1 (Compound 6) is a potent inhibitor of AChE/Hca with IC50 values of 22.21, 60.79 and 66.64 nM for AChE, Hca Ⅰ and Hca Ⅱ. AChE/hCA I/II-IN-1 can be used for the rsearch for glaucoma, Alzheimer's disease, diabetes[1].

  • CAS Number: 2049681-10-7
  • MF: C15H13N3S
  • MW: 267.35
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Itraconazole-d5

Itraconazole-d5 (R51211-d5) is the deuterium labeled Itraconazole. Itraconazole (R51211) is a triazole antifungal agent and a potent and orally active Hedgehog (Hh) signaling pathway antagonist with an IC50 of ~800 nM. Itraconazole potently inhibits lanosterol 14α-demethylase (cytochrome P450 enzyme), thereby inhibits the oxidative conversion of lanosterol to ergosterol. Itraconazole has anticancer and antiangiogenic effects[1][2][3].

  • CAS Number: 1217510-38-7
  • MF: C35H33Cl2D5N8O4
  • MW: 710.66400
  • Catalog: Fungal
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PCSK9-IN-17

PCSK9-IN-17 is a PCSK9 inhibitor. PCSK9-IN-17 can be used for the research of cholesterol metabolism (WO2020150474A1, compound 105)[1].

  • CAS Number: 2455424-72-1
  • MF: C16H19N5OS
  • MW: 329.42
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

sPLA2 inhibitor 1

sPLA2 inhibitor 1, a D-tyrosine derivative, is an orally active, potent secretory phospholipase A2 (sPLA2) inhibitor with an IC50 of 29 nM for human nonpancreatic secretory PLA2 isoform IIa (hnpsPLA2-IIa). sPLA2 inhibitor 1 has anti-inflammatory activity[1].

  • CAS Number: 393569-31-8
  • MF: C31H37NO4
  • MW: 487.63
  • Catalog: Phospholipase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 720.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 389.8±32.9 °C

Filaminast

WAY-PDA 641 is a potent and preferential PDE-IV inhibitor, with an IC50 of 0.42 μM for canine trachealis PDE-IV. WAY-PDA 641 induces respiratory muscle relaxation and bronchodilation[1].

  • CAS Number: 141184-34-1
  • MF: C15H20N2O4
  • MW: 292.33000
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.25g/cm3
  • Boiling Point: 432.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 215.1ºC

DPP IV/hCA II-IN-1

DPP IV/hCA II-IN-1 is a potent and selective dipeptidyl peptidase IV (DPP IV) and carbonic anhydrase (CA) inhibitor with an IC50 value of 0.049 μM for DPP IV and with Ki values of 0.0361, 0.0428, 0.0941, 0.1328, 0.2615, and 3.034 μM for CA II, CA VB, CA VA, CA IX, CA I, and CA IV, respectively[1].

  • CAS Number: 2836996-95-1
  • MF: C17H20N2O5S
  • MW: 364.42
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IDO1-IN-2

IDO1-IN-2 (compound 16) is a potent and selective IDO1 inhibitor with IC50s of 81 nM, 59 nM (mouse) and 28 nM (rat), respectively. IDO1-IN-2 has anti-cancer activity[1].

  • CAS Number: 2346614-58-0
  • MF: C15H17FN6O4
  • MW: 364.33
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ximelagatran

Ximelagatran (H 376/95) is an orally active thrombin inhibitor that selectively and competitively inhibits both free and clot-bound thrombin. Ximelagatran is an anticoagulant agent with a rapid onset of anticoagulant effect, predictable, dose-dependent pharmcokinetics and pharmacodynamics[1][2].

  • CAS Number: 192939-46-1
  • MF: C24H35N5O5
  • MW: 473.565
  • Catalog: Thrombin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phortress free base

Phortress free base (NSC 710305) is a P450 CYP1A1-activated antitumor prodrug with antitumor activity[1]. Phortress free base leads to DNA damage and cell cycle arrest[2].

  • CAS Number: 741241-36-1
  • MF: C20H23FN4OS
  • MW: 386.49
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(±)-trans-GK563

GK563 is a selective Ca2+-independent phospholipase A2 (GVIA iPLA2) inhibitor with an IC50 value of 1 nM. GK563 is 22000 times more active against GVIA iPLA2 than GIVA cPLA2. GK563 reduces β-cell apoptosis induced by proinflammatory cytokines, raising the possibility that it can be beneficial in countering autoimmune diseases, such as type 1 diabetes[1].

  • CAS Number: 2351820-19-2
  • MF: C16H22O2
  • MW: 246.345
  • Catalog: Apoptosis
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 364.2±11.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 152.3±16.7 °C

Dolutegravir Sodium

Dolutegravir sodium is an inhibitor of HIV-1 integrase-catalyzed strand transfer with IC50 of 2.7 nM.

  • CAS Number: 1051375-19-9
  • MF: C20H18F2N3NaO5
  • MW: 441.361
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

K-604 dihydrochloride

K-604 dihydrochloride is a potent and selective acyl-CoA:cholesterol acyltransferase 1 (ACAT-1) inhibitor with an IC50 of 0.45±0.06 μM.

  • CAS Number: 217094-32-1
  • MF: C23H32Cl2N6OS3
  • MW: 575.64
  • Catalog: Acyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SHP099

SHP099 is a potent, selective, orally available SHP2 inhibitor with an IC50 of 70 nM.

  • CAS Number: 1801747-42-1
  • MF: C16H19Cl2N5
  • MW: 352.262
  • Catalog: Phosphatase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 530.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.5±30.1 °C

DPP-4/GPR119 modulator 1

DPP-4/GPR119 modulator 1 (Compound 22) is an orally active dipeptidyl peptidase IV (DPP-IV) inhibitor and GPR119 agonist. DPP-4/GPR119 modulator 1 shows blood glucose-lowering effect and moderate inhibition on hERG channel with an IC50 of 4.9 µM. DPP-4/GPR119 modulator 1 can be used for diabetes research[1][1].

  • CAS Number: 2411099-68-6
  • MF: C30H39ClN10O3
  • MW: 623.15
  • Catalog: GPR119
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDK2-IN-11

CDK2-IN-11 (compound 9d) is a potent CDK2 inhibitor with an IC50 of 6.4 μM, and KI values of 23.4 nM, 56.3 nM and 44.3 nM for hCA II, hCA IX and hCA XII, respectively. CDK2-IN-11 can be used for researching anticancer[1].

  • CAS Number: 2410402-82-1
  • MF: C18H14ClN7O2S
  • MW: 427.87
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A