Stem cells are required for continuous tissue maintenance within diverse organs, stem cell activity is often externally dictated by the microenvironment (the niche) so that stem cell output is precisely shaped to meet homeostatic needs or regenerative demands. Several key signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the JAK/STAT, Hedgehog, Wnt, Notch, Smad, PI3K/phosphatase and tensin homolog, and NK-κB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation.

Recent studies mainly focus on cancer stem cell, induced pluripotent stem cell, neural stem cell and maintenance of embryonic stem cell pluripotency. Cancer stem cells (CSCs) have been believed to be responsible for tumor initiation, growth, and recurrence. Numerous agents have been developed to specifically target CSCs by suppressing the expression of pluripotency maintaining factors Nanog, Oct-4, Sox-2, and c-Myc and transcription of GLI. Induced pluripotent stem cells (iPSCs) have the capacity to differentiate into various types of cells, and a self-renewing resource, and scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Novel pathological mechanisms have been elucidated, new drugs originating from iPSC screens are in the pipeline and the first clinical trial using human iPSC-derived products has been initiated.

References:
[1] Clevers H, et al. Science. 2014 Oct 3;346(6205):1248012.
[2] Matsui WH. Medicine (Baltimore). 2016 Sep;95(1 Suppl 1):S8-S19.
[3] Koury J, et al. Stem Cells Int. 2017;2017:2925869.
[4] Garg A, et al. Cells. 2017 Feb 2;6(1). doi: 10.3390/cells6010004.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
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Cell Cycle/DNA Damage >
Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
Cytoskeleton >
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Epigenetics >
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GPCR/G Protein >
5-HT Receptor Adenosine Receptor Adenylate Cyclase Adiponectin Receptor Adrenergic Receptor Angiotensin Receptor Bombesin Receptor Bradykinin Receptor Cannabinoid Receptor CaSR CCR CGRP Receptor Cholecystokinin Receptor CRFR CXCR Dopamine Receptor EBI2/GPR183 Endothelin Receptor GHSR Glucagon Receptor Glucocorticoid Receptor GNRH Receptor GPCR19 GPR109A GPR119 GPR120 GPR139 GPR40 GPR55 GPR84 Guanylate Cyclase Histamine Receptor Imidazoline Receptor Leukotriene Receptor LPL Receptor mAChR MCHR1 (GPR24) Melatonin Receptor mGluR Motilin Receptor Neurokinin Receptor Neuropeptide Y Receptor Neurotensin Receptor Opioid Receptor Orexin Receptor (OX Receptor) Oxytocin Receptor P2Y Receptor Prostaglandin Receptor Protease-Activated Receptor (PAR) Ras RGS Protein Sigma Receptor Somatostatin Receptor TSH Receptor Urotensin Receptor Vasopressin Receptor Melanocortin Receptor
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JAK/STAT Signaling >
EGFR JAK Pim STAT
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
Membrane Transporter/Ion Channel >
ATP Synthase BCRP Calcium Channel CFTR Chloride Channel CRAC Channel CRM1 EAAT2 GABA Receptor GlyT HCN Channel iGluR Monoamine Transporter Monocarboxylate Transporter Na+/Ca2+ Exchanger Na+/HCO3- Cotransporter Na+/K+ ATPase nAChR NKCC P-glycoprotein P2X Receptor Potassium Channel Proton Pump SGLT Sodium Channel TRP Channel URAT1
Metabolic Enzyme/Protease >
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
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
PROTAC E3 Ligase Ligand-Linker Conjugate Ligand for E3 Ligase PROTAC Linker PROTAC-linker Conjugate for PAC
Protein Tyrosine Kinase/RTK >
Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
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Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
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TGF-beta/Smad PKC ROCK TGF-β Receptor
Vitamin D Related >
VD/VDR
Others >
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SEN461

SEN461 is a wnt inhibitor.

  • CAS Number: 1287727-28-9
  • MF: C25H34N4O6
  • MW: 486.56
  • Catalog: Wnt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Synaptamide

Synaptamide is a potent mediator for neurogenic differentiation of NSCs acting through PKA/CREB activation.Target: in vitro: Synaptamide inhibits forskolin-mediated cAMP production (IC50 =6 μM) in CHO-HCR cells. Synaptamide decreases the viability of the LNCaP and PC3 prostate cancer cell lines (IC50=120-130 μM) grown in media containing 10% fetal bovine serum. [1] Synaptamide is an endogenous DHA metabolite with endocannabinoid-like structure, promotes neurite growth, synaptogenesis and synaptic function. Synaptamide potently induces neuronal differentiation of NSCs. Treatment of NSCs with Synaptamide at low nanomolar concentrations significantly increased the number of MAP2 and Tuj-1 positive neurons with concomitant induction of PKA/CREB phosphorylation. [2]

  • CAS Number: 162758-94-3
  • MF: C24H37NO2
  • MW: 371.556
  • Catalog: PKA
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 544.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 283.3±30.1 °C

Y-27632

Y-27632 is an ATP-competitive inhibitor of ROCK-I and ROCK-II, with Ki of 220 nM and 300 nM for ROCK-I and ROCK-II, respectively.

  • CAS Number: 146986-50-7
  • MF: C14H21N3O
  • MW: 247.34
  • Catalog: ROCK
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 462.6±15.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.6±20.4 °C

TIC10

TIC10 is a potent, orally active, and stable TRAIL inducer, also inhibits Akt and ERK activity.

  • CAS Number: 1616632-77-9
  • MF: C24H26N4O
  • MW: 386.489
  • Catalog: TNF Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 559.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 292.3±32.9 °C

Fluticasone

Fluticasone is an inhaled corticosteroid used for respiratory diseases[1]. Fluticasone is a Smo agonist s with a IC50 value of 99 nM. Fluticasone activate Hedgehog signaling and promotes the proliferation of primary neuronal stem/precursor cells[2].

  • CAS Number: 90566-53-3
  • MF: C25H31F3O5S
  • MW: 500.571
  • Catalog: Glucocorticoid Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 568.3±50.0 °C at 760 mmHg
  • Melting Point: -18.1ºC
  • Flash Point: 297.5±30.1 °C

cerdulatinib

Cerdulatinib (PRT062070) is a dual JAK and SYK inhibitor with IC50s of 12, 6, 8 and 32 for JAK1, 2, 3 and SYK, respectively.

  • CAS Number: 1198300-79-6
  • MF: C20H27N7O3S
  • MW: 445.539
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 741.9±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 402.5±35.7 °C

VP3.15

VP3.15 is a potent, orally bioavailable and CNS-penetrant dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, with IC50s of 1.59 μM and 0.88 μM for PDE7 and GSK-3, respectively. VP3.15 has neuroprotective and neuroreparative activities, thus as potential combined anti-inflammatory and pro-remyelinating therapies for multiple sclerosis (MS)[1].

  • CAS Number: 1281681-54-6
  • MF: C20H22N4OS
  • MW: 366.48
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KYA 1797K

KYA1797K is a potent and selective Wnt/β-catenin inhibitor with an IC50 of 0.75 µM.

  • CAS Number: 1956356-56-1
  • MF: C17H11KN2O6S2
  • MW: 442.507
  • Catalog: Wnt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YW1128

YW1128 is an inhibitor of Wnt/��-catenin signaling with an IC50 value of 4.1 nM in a reporter assay.

  • CAS Number: 2131223-64-6
  • MF: C20H17N5O
  • MW: 343.382
  • Catalog: Wnt
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-06700841

PF-06700841 is a dual JAK1 and TYK2 inhibitor with IC50s of 17 and 23 nM, respectively. Anti-inflammatory activity[1].

  • CAS Number: 1883299-62-4
  • MF: C18H21F2N7O
  • MW: 389.40
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FLLL32

FLLL32 is a STAT3 inhibitor derived from the natural product curcumin. FLLL32 retains the cellular response to cytokines with anti-tumor activity[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UC-514321

UC-514321 is a more effective analog of NSC-370284 that directly binds to STAT3/5, significantly and selectively suppresses the viability of AML cells with high level of TET1 expression both in vitro and in vivo; shows no inhibitory effect on the viability of TET1-low AML (i.e., NB4) cells, function as TET1-transcription inhibitor in TET1-high AMLs and the anti-leukemic effects are TET1-dependent.

  • CAS Number: 299420-83-0
  • MF: C26H35NO5
  • MW: 441.568
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RUSKI-201 dihydrochloride

RUSKI-201 dihydrochloride is a potent and specific Hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 0.20 μM. RUSKI-201 dihydrochloride is able to block Hh signaling from Shh overexpressing cells and inhibits Hh palmitoylation. RUSKI-201 dihydrochloride is potential Hhat chemical probe in cells and can used in studies of Hhat catalytic function[1].

  • CAS Number: 2320262-09-5
  • MF: C20H29Cl2N3OS
  • MW: 430.43
  • Catalog: Hedgehog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HA-100 hydrochloride

HA-100 hydrochloride is a potent protein kinase inhibitor, with IC50s of 4 μM, 8 μM, 12 μM and 240 μM for cGMP-dependent protein kinase (PKG), cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and MLC-kinase, respectively. HA-100 hydrochloride also used as a ROCK inhibitor[1][2].

  • CAS Number: 141543-63-7
  • MF: C13H16ClN3O2S
  • MW: 313.80300
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: 497.4ºC at 760 mmHg
  • Melting Point: 252-254ºC
  • Flash Point: 254.6ºC

NSC260594

NSC260594 (NSC 260594) is a specific inhibitor of HIV-1 RNA packaging, which involves preventing the interaction of Gag with SL3 by stabilizing this small RNA stem-loop which then leads to stabilization of the global packaging signal region (psi or ψ); specifically blocks HIV-1 RNA encapsidation, binds to HIV-1 gRNA and exhibits potent antiviral activity; NSC260594 also is a small molecule inhibitor of the Escherichia coli condensin MukBEF, affects MukB directly.

  • CAS Number: 906718-66-9
  • MF: C29H24N6O3
  • MW: 504.55
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CK2-IN-4

CK2-IN-4 (compound 5) is a protein kinase (CK2) inhibitor (IC50=8.6 µM). CK2-IN-4 has good potential for research in the areas of cancer, viral infections and glomerulonephritis[1].

  • CAS Number: 313985-59-0
  • MF: C18H11N3O4S
  • MW: 365.36264
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Disitertide

Disitertide is an inhibitor of TGF-β1. Sequence: Thr-Ser-Leu-Asp-Ala-Ser-Ile-Ile-Trp-Ala-Met-Met-Gln-Asn.

  • CAS Number: 272105-42-7
  • MF: C68H109N17O22S2
  • MW: 1580.82000
  • Catalog: Peptides
  • Density: 1.327g/cm3
  • Boiling Point: 1968.718ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: N/A

MYF-01-37

MYF-01-37 is a covalent TEAD inhibitor targeting Cys380. MYF-01-37 has a reversible inhibition on YAP/TEAD interaction[1].

  • CAS Number: 2416417-65-5
  • MF: C15H17F3N2O
  • MW: 298.30
  • Catalog: YAP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Enoticumab

Enoticumab (REGN421, SAR153192) is an IgG1κ antibody targeting human Dll4. DLL4 is a ligand of the Notch signaling pathway and regulates fatty acid uptake through non-transcriptional regulation of macropinocytosis-dependent long-chain fatty acid uptake. Specific in vivo activity of Enoticumab in an ovarian xenograft model. EGN421 (2.5 mg/kg once weekly) resulted in 86% and 83% tumor growth inhibition in mouse subcutaneous TOV-112D or intraperitoneal A2780 human tumor xenograft models, respectively[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNJ-6204

JNJ-6204 is a dual inhibitor for CSNK1D (Casein Kinase 1 Delta) and CSNK1E (Casein Kinase 1 Epsilon) (CSNK1D IC50=2.3 nM; CSNK1E IC50=137 nM). JNJ-6204 shows good brain exposure[1][2].

  • CAS Number: 2765264-50-2
  • MF: C19H11D6FN6O
  • MW: 370.41
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SGC-CK2-1

SGC-CK2-1 is a highly potent, ATP-competitive, and cell-active CK2 chemical probe with exclusive selectivity for both human CK2 isoforms, with IC50s of 36 and 16 nM for CK2α and CK2α′respectively in the nanoBRET assay. SGC-CK2-1 can be used for the research of neurodegenerative diseases[1][2].

  • CAS Number: 2470424-39-4
  • MF: C20H21N7O
  • MW: 375.43
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK/HDAC-IN-1

JAK/HDAC-IN-1 is a potent JAK2/HDAC dual inhibitor, exhibits antiproliferative and proapoptotic activities in several hematological cell lines. JAK/HDAC-IN-1 shows IC50s of 4 and 2 nM for JAK2 and HDAC, respectively[1].

  • CAS Number: 2284621-75-4
  • MF: C19H21Cl2N7O2
  • MW: 450.32
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ROCK-IN-5

ROCK-IN-5 (compound I-B-37) is a potent inhibitor of ROCK, ERK, GSK, and AGC protein kinases. ROCK-IN-5 has the potential for proliferative, cardiac and neurodegenerative diseases research[1].

  • CAS Number: 692870-25-0
  • MF: C16H11ClFN3OS
  • MW: 347.79
  • Catalog: ROCK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB216763

SB 216763 is potent, selective and ATP-competitive GSK-3 inhibitor with IC50s of 34.3 nM for both GSK-3α and GSK-3β.

  • CAS Number: 280744-09-4
  • MF: C19H12Cl2N2O2
  • MW: 371.217
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 598.1±50.0 °C at 760 mmHg
  • Melting Point: 287-288.6ºC(lit.)
  • Flash Point: 315.5±30.1 °C

AR-13324 (hydrochloride)

Netarsudil hydrochloride is a ROCK, and norepinephrine transporter inhibitor. Target: ROCKin vitro: AR-13324 is a small-molecule inhibitor of Rho kinase and a norepinephrine transporter; reduces intraocular pressure (IOP) in normotensive monkey eyes.[1] AR-13324 is a small-molecule inhibitor of Rho kinase and a norepinephrine transporter.[2]in vivo: AR-13324 produces statistically significant lowering of episcleral venous pressure (EVP) in Dutch Belted (DB) rabbits. [3]

  • CAS Number: 1253952-02-1
  • MF: C28H29Cl2N3O3
  • MW: 526.454
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gsk270822a

GSK270822A is a selective ROCK1 inhibitor. GSK270822A exhibits IC50 of 9nM, 1100nM, 1550nM for ROCK1, RSK1, p70S6K, respectively.

  • CAS Number: 864082-23-5
  • MF: C24H20N4O2
  • MW: 396.44
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RP106

Aloisine RP106 (compound 38) is a potent inhibitor of Cdk1/cyclin B, Cdk5/p25, and GSK3 with IC50s of 0.70µM, 1.5µM, 0.92 µM, respectively[1].

  • CAS Number: 496864-15-4
  • MF: C16H17N3O
  • MW: 267.32600
  • Catalog: CDK
  • Density: 1.155g/cm3
  • Boiling Point: N/A
  • Melting Point: 182-184ºC
  • Flash Point: N/A

PM-81I

PM-81I is a potent STAT6 inhibitor (targeting the SH2 structural domain) that effectively reduces STAT6 phosphorylation levels. PM-81I can be used in studies of allergic lung disease, allergic rhinitis, chronic obstructive pulmonary disease or cancer[1].

  • CAS Number: 1637532-83-2
  • MF: C43H58F2N3O10P
  • MW: 845.91
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALLO-2

ALLO-2 is a potent drug-resistant Smoothened (Smo) mutant antagonist that inhibits Smo agonist Hh-Ag1.5-induced luciferase expression in TM3-Gli-Luc cells with IC50 of 6 nM[1].

  • CAS Number: 1357350-60-7
  • MF: C18H12F3N5O
  • MW: 371.32
  • Catalog: Smo
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bilobetin

Bilobetin, an active component of Ginkgo biloba, can reduce blood lipids and improve the effects of insulin. Bilobetin ameliorated insulin resistance, increased the hepatic uptake and oxidation of lipids, reduced very-low-density lipoprotein triglyceride secretion and blood triglyceride levels, enhanced the expression and activity of enzymes involved in β-oxidation and attenuated the accumulation of triglycerides and their metabolites in tissues. Bilobetin also increased the phosphorylation, nuclear translocation and activity of PPARα accompanied by elevated cAMP level and PKA activity[1].

  • CAS Number: 521-32-4
  • MF: C31H20O10
  • MW: 552.484
  • Catalog: PPAR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 869.9±65.0 °C at 760 mmHg
  • Melting Point: 296-298ºC
  • Flash Point: 291.9±27.8 °C