MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. In mammalian cells, three MAPK families have been clearly characterized: namely classical MAPK (ERK), C-Jun N-terminal kinse/ stress-activated protein kinase (JNK/SAPK) and p38 kinase. Each MAPK-related cascade consists of no fewer than three enzymes that are activated in series: a MAPK kinase kinase (MAPKKK), a MAPK kinase (MAPKK) and a MAP kinase (MAPK).

The MAPK pathways are activated by diverse extracellular and intracellular stimuli including peptide growth factors, cytokines, hormones, and various cellular stressors. In the ERK signaling pathway, ERK1/2 is activated by MEK1/2, which is activated by Raf. Raf is activated by the Ras GTPase, whose activation is induced by RTKs such as the epidermal growth factor receptor. The JNK and p38 MAPK signaling pathways are activated by various types of cellular stress. The JNK pathway consists of JNK, a MAP2K such as MKK4 (SEK1) or MKK7, and a MAP3K such as ASK1, TAK1, MEKK1, or MLK3. In the p38 pathway, p38 is activated by MKK3 or MKK6, and these MAP2Ks are activated by the same MAP3Ks that function in the JNK pathway.

MAPK signaling pathways has been implicated in the development of many human diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and various types of cancers. Therefore, the development of small molecule drugs that selectively inhibit individual components of MAPK signaling pathways is a key therapeutic strategy for cancer and neurodegenerative disorders.

References:
[1] Zhang W, et al. Cell Research (2002) 12, 9-18.
[2] Kim EK, et al. Biochim Biophys Acta. 2010 Apr;1802(4):396-405.
[3] Kim EK, et al. Arch Toxicol. 2015 Jun;89(6):867-82.


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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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
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JAK/STAT Signaling >
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
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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 >
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NF-κB >
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PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
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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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VD/VDR
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p38α inhibitor 4

p38α inhibitor 4 (compound 10) is a selective and allosteric p38α inhibitor with an IC50 value of 1.2 μM. p38α inhibitor 4 exhibits no activity against p38β, p38γ, and p38δ[1].

  • CAS Number: 1262406-08-5
  • MF: C14H7F6N3O
  • MW: 347.22
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4′-Demethylnobiletin

4′-Demethylnobiletin is a bioactive metabolite that activates the PKA/ERK/CREB signaling pathway, enhances CRE-mediated transcription in hippocampal neurons, and reverses memory impairment associated with NMDA receptor antagonism by stimulating ERK signaling[1].

  • CAS Number: 34810-62-3
  • MF: C20H20O8
  • MW: 388.36800
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tauroursodeoxycholate-d4-1

Tauroursodeoxycholate-d4-1 is the deuterium labeled Tauroursodeoxycholate. Tauroursodeoxycholate (Tauroursodeoxycholic acid) is an endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.

  • CAS Number: 2573035-17-1
  • MF: C26H41D4NO6S
  • MW: 503.73
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vemurafenib (PLX4032)

Vemurafenib is a novel and potent inhibitor of B-RAF kinase, with IC50s of 31 and 48 nM for RAFV600E and c-RAF-1, respectively.

  • CAS Number: 918504-65-1
  • MF: C23H18ClF2N3O3S
  • MW: 489.922
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 711.4±70.0 °C at 760 mmHg
  • Melting Point: 260-262 °C
  • Flash Point: 384.0±35.7 °C

HPK1-IN-8

HPK1-IN-8 is an allosteric, inactive conformation-selective inhibitor of full-length HPK1.

  • CAS Number: 1214561-09-7
  • MF: C19H17FN6O2S
  • MW: 412.44
  • Catalog: MAP4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trametinib (GSK1120212)

Trametinib is a potent MEK inhibitor that inhibits MEK1 and MEK2 with IC50s of about 2 nM. Due to the poor solubility of Trametinib, Trametinib DMSO solvate (Cat. No.: HY-10999A) is recommeded.

  • CAS Number: 871700-17-3
  • MF: C26H23FIN5O4
  • MW: 615.395
  • Catalog: MEK
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RAF265 (CHIR-265)

RAF265 is a potent RAF/VEGFR2 inhibitor.

  • CAS Number: 927880-90-8
  • MF: C24H16F6N6O
  • MW: 518.414
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 667.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.5±34.3 °C

Peraquinsin

Peraquinsin is a MK2 activator. Peraquinsin can be used for the research of vascular disorder or endothelial barrier disorder. Peraquinsin also is an antihypertensive agent[1].

  • CAS Number: 35265-50-0
  • MF: C23H28N4O4
  • MW: 424.49300
  • Catalog: MAPKAPK2 (MK2)
  • Density: 1.27g/cm3
  • Boiling Point: 613.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 324.9ºC

PF-4708671

PF-4708671 is a potent cell-permeable S6K1 inhibitor with a Ki of 20 nM and IC50 of 160 nM.

  • CAS Number: 1255517-76-0
  • MF: C19H21F3N6
  • MW: 390.405
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 572.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 300.2±30.1 °C

Anti-inflammatory agent 33

Anti-inflammatory agent 33 is a potent p38α inhibitor. Anti-inflammatory agent 33 inhibits NO production. Anti-inflammatory agent 33 inhibits LPS-induced iNOS, COX-2, p-p38α, p-MK2 protein expression. Anti-inflammatory agent 33 shows anti-inflammatory activity[1].

  • CAS Number: 2816993-09-4
  • MF: C22H15N3O5S
  • MW: 433.44
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

n-Butyl α-D-fructofuranoside

n-Butyl α-D-fructofuranoside, isolated from the root barks of Ulmus davidiana var. japonica, enhances Nrf2 activity through activation of JNK and has antiinflammation activity[1][2].

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

B-Raf IN 15

B-Raf IN 15 (Compound 7) is a BRAF inhibitor. B-Raf IN 15 inhibits BRAF WT and BRAF V600E with IC50s of 2.0 and 0.8 μM. B-Raf IN 15 can be used for the research of cancer[1].

  • CAS Number: 832107-31-0
  • MF: C19H15N3OS
  • MW: 333.41
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-PD 0325901CL

(R)-PD 0325901CL is an isomer of PD 0325901CL. PD 0325901CL is a selective inhibitor of mitogen-activated protein kinase kinase (MEK) involved in cancer research. PD 0325901CL inhibits the growth of cancer cells in vitro and in vivo[1].

  • CAS Number: 1003216-77-0
  • MF: C16H14ClF2IN2O4
  • MW: 498.64800
  • Catalog: MEK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Takinib

Takinib is a potent and selective TAK1 inhibitor with an IC50 of 9.5 nM.

  • CAS Number: 1111556-37-6
  • MF: C18H18N4O2
  • MW: 322.36
  • Catalog: MAP3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 706504

SB 706504 is a potent p38 MAPK inhibitor that inhibits Lipopolysaccharides (HY-D1056)-stimulated inflammatory gene expression in macrophages in chronic obstructive pulmonary disease (COPD)[1].

  • CAS Number: 911110-38-8
  • MF: C24H19F3N8O
  • MW: 492.456
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC-401

CC-401 hydrochloride is a potent inhibitor of all three forms of JNK with Ki of 25 to 50 nM.

  • CAS Number: 1438391-30-0
  • MF: C22H25ClN6O
  • MW: 424.927
  • Catalog: JNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zeatin

(E/Z)-Zeatin is a plant cytokinin, which plays an important role in cell growth, differentiation, and division; (E/Z)-Zeatin also inhibits UV-induced MEK/ERK activation.

  • CAS Number: 13114-27-7
  • MF: C10H13N5O
  • MW: 219.24
  • Catalog: ERK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 395.0±52.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 192.7±30.7 °C

SW-083688

SW-083688 (SW083688) is a potent, highly selective TAOK2 (Thousand-And-One Kinase 2, MAP3K17) inhibitor with IC50 of 1.3 uM; increases the abundance of p62 and inhibits autophagy; TAOK2 is an activator of p38 MAP kinase cascade that is up-regulated in response to environmental stresses, and a potential cancer therapeutic target.

  • CAS Number: 422281-45-6
  • MF: C23H25N3O5S
  • MW: 455.529
  • Catalog: MAP3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB-682330A

SB-682330A is a Raf kinase inhibitor.

  • CAS Number: 502498-66-0
  • MF: C28H27N3O3
  • MW: 453.53
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lidocaine

Lidocaine, an amide local anesthetic, has anti-inflammatory properties in vitro and in vivo, possibly due to an attenuation of pro-inflammatory cytokines, intracellular adhesion molecule-1 (ICAM-1), and reduction of neutrophils influx.Target: Lidocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery. Lidocaine, the first amino amide–type local anesthetic, was first synthesized under the name xylocaine by Swedish chemist Nils Lofgren in 1943. His colleague Bengt Lundqvist performed the first injection anesthesia experiments on himself.Lidocaine is approximately 95% metabolized (dealkylated) in the liver by CYP3A4 to the pharmacologically-active metabolites monoethylglycinexylidide (MEGX) and then subsequently to the inactive glycine xylidide. MEGX has a longer half life than lidocaine but also is a less potent sodium channel blocker. The elimination half-life of lidocaine is approximately 90–120 minutes in most patients. This may be prolonged in patients with hepatic impairment (average 343 minutes) or congestive heart failure (average 136 minutes).

  • CAS Number: 137-58-6
  • MF: C14H22N2O
  • MW: 234.337
  • Catalog: Apoptosis
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 372.7±52.0 °C at 760 mmHg
  • Melting Point: 66-69°C
  • Flash Point: 179.2±30.7 °C

ERK5-IN-5

ERK5-IN-5 (compound 4a) is an ERK5 kinase inhibitor with anticancer activity. ERK5-IN-5 exhibits good anti-proliferative activity with the IC50 value of 6.23 µg/mL for A549 cells[1].

  • CAS Number: 2318792-30-0
  • MF: C19H16ClN3O
  • MW: 337.80
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HIOC

HIOC is a potent and selective activator of TrkB (tropomyosin related kinase B) receptor. HIOC can pass the blood-brain and blood-retinal barriers.HIOC activates TrkB/ERK pathway and decreases neuronal cell apoptosis. HIOC attenuates early brain injury after SAH (subarachnoid hemorrhage). HIOC shows protective activity in an animal model for light-induced retinal degeneration[1][2][3].

  • CAS Number: 314054-36-9
  • MF: C16H19N3O3
  • MW: 301.34
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 746.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 405.0±32.9 °C

A-196

AD80, a multikinase inhibitor, inhibits RET, RAF,SRCand S6K, with greatly reduced mTOR activity.

  • CAS Number: 1384071-99-1
  • MF: C22H19F4N7O
  • MW: 473.433
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNK-IN-7

JNK-IN-7 is a potent JNK inhibitor with IC50 of 1.5, 2 and 0.7 nM for JNK1, JNK2 and JNK3, respectively.

  • CAS Number: 1408064-71-0
  • MF: C28H27N7O2
  • MW: 493.560
  • Catalog: JNK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BRAF-V600E degrader-2

PROTAC BRAF-V600E degrader-2 (compound 12) is a potent BRAF-V600E degrader with Kds of 14.4 nM and 9.5 nM for BRAF and BRAF-V600E, respectively. PROTAC BRAF-V600E degrader-2 selectively degraded the kinase domain of BRAF-V600E but not the wild-type BRAF. PROTAC BRAF-V600E degrader-2 inhibits melanoma cell growth[1].

  • CAS Number: 2417296-82-1
  • MF: C42H39F2N7O8S
  • MW: 839.86
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NQDI 1

NQDI-1 inhibits apoptosis signal-regulating kinase 1 (ASK1) with a Ki of 500 nM and an IC50 of 3 μM.

  • CAS Number: 175026-96-7
  • MF: C19H13NO4
  • MW: 319.311
  • Catalog: MAP3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 581.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.4±30.1 °C

Bupivacaine hydrochloride

Bupivacaine Hydrochloride is a local anaesthetic drug belonging to the amino amide group.Target: OthersBupivacaine hydrochloride is an effective local anesthetic agent. It has a rapid onset time, a high frequency of surgical anesthesia, a long duration, and a low incidence of side effects [1]. Median doses of bupivacaine (in milligrams per kilogram) producing asystole in protocol 1 were for 17.7 for saline, 27.6 for 10% Intralipid, 49.7 for 20% Intralipid, and 82.0 for 30% Intralipid (P < 0.001 for differences between all groups). Differences in mean +/- SE concentrations of bupivacaine in plasma (in micrograms per milliliter) were significant (P < 0.05) for the difference between saline (93.3 +/- 7.6) and 30% Intralipid (212 +/- 45). In protocol 2, lipid infusion increased the dose of bupivacaine required to cause death in 50% of animals by 48%, from 12.5 to 18.5 mg/kg. The mean lipid:aqueous ratio of concentrations of bupivacaine in a plasma-Intralipid mixture was 11.9 +/- 1.77 (n = 3) [2].

  • CAS Number: 18010-40-7
  • MF: C18H29ClN2O
  • MW: 324.889
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: N/A
  • Boiling Point: 423.4ºC at 760 mmHg
  • Melting Point: 107.5 to 108ºC
  • Flash Point: 209.9ºC

ITX5061

ITX5061 is a type II inhibitor of p38 MAPK and also an antagonist of scavenger receptor B1 (SR-B1).

  • CAS Number: 1252679-52-9
  • MF: C30H38ClN3O7S
  • MW: 620.15700
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

astin B

Astin B is a orally active and potent cyclic pentapeptide, that can be isolated from Aster tataricus. Astin B has hepatotoxic effects in vitro and in vivo and that hepatic injury was primarily mediated by apoptosis in a mitochondria/caspase-dependent manner. Astin B induces autophagy in L-02 cells, increases LC3-II and decreases p62 expression[1].

  • CAS Number: 151201-76-2
  • MF: C25H33Cl2N5O7
  • MW: 586.46
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Atraric acid

Atraric acid (Methyl atrarate) is a specific androgen receptor (AR) antagonist with anti-inflammatory and anticancer effects. Atraric acid represses the expression of the endogenous prostate specific antigen gene in both LNCaP and C4-2 cells. Atraric acid can also inhibit the synthesis of NO and cytokine, and suppress the MAPK-NFκB signaling pathway. Atraric acid can be used to research prostate diseases and inflammatory diseases[1][2].

  • CAS Number: 4707-47-5
  • MF: C10H12O4
  • MW: 196.200
  • Catalog: NO Synthase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 360.7±22.0 °C at 760 mmHg
  • Melting Point: 141-146 °C(lit.)
  • Flash Point: 143.9±15.8 °C