The p53 tumor suppressor is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage. p53 is a short-lived protein that is maintained at low, often undetectable, levels in normal cells. Under stress conditions, the p53 protein accumulates in the cell, binds in its tetrameric form to p53-response elements and induces the transcription of various genes. MDM-2 is transcriptionally activated by p53 and MDM-2, in turn, inhibits p53 activity in several ways. MDM-2 binds to the p53 transactivation domain and thereby inhibits p53-mediated transactivation. MDM-2 also contains a signal sequence that is similar to the nuclear export signal of various viral proteins and, after binding to p53, it induces its nuclear export. As p53 is a transcription factor, it needs to be in the nucleus to be able to access the DNA; its transport to the cytoplasm by MDM-2 prevents this. Finally, MDM-2 is a ubiquitin ligase, so is able to target p53 for degradation by the proteasome. In many tumors p53 is inactivated by the overexpression of the negative regulators MDM2 and MDM4 or by the loss of activity of the MDM2 inhibitor ARF. The pathway can be reactivated in these tumors by small molecules that inhibit the interaction of MDM2 and/or MDM4 with p53. Such molecules are now in clinical trials.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
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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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NSC59984

NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. The EC50 of NSC59984 in most cancer cells is significantly lower than those of normal cells, with EC50 of 8.38 μM for p53-null HCT116 cells.IC50 value: 8.38 μM (EC50, for p53-null HCT116 cells)Target: p53in vitro: NSC59984 specifically restores p53 pathway signaling in mutant p53-expressing human colorectal cancer cells. NSC59984 induces cell death in tumor cells but not normal cells with little or no genotoxicity. NSC59984 induces mutant p53 protein degradation through MDM2-mediated ubiquitination in cancer cells. NSC59984 restores p53 pathway signaling through activation of p73. NSC59984 induces p73-dependent cell apoptosis in cancer.in vivo: NSC59984 synergizes with CPT11 to induce cell death in mutant p53-expressing colorectal cancer cells and inhibits mutant p53-associated colon tumor xenograft growth in a p73-dependent manner.

  • CAS Number: 803647-40-7
  • MF: C12H15N3O4
  • MW: 265.265
  • Catalog: MDM-2/p53
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 451.8±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 227.1±28.7 °C

MeOIstPyrd

MeOIstPyrd is an anti-skin cancer agent. MeOIstPyrd inhibits cell proliferation, migration, and spheroid formation by activating the mitochondrial intrinsic apoptotic pathway. MeOIstPyrd induces DNA damage. MeOIstPyrd activates p53, and increases the half-life of p53 and stabilizes p53 by phosphorylating it at ser15. MeOIstPyrd binds to MDM2 in the p53 sub-pocket and blocks p53-MDM2 interaction[1].

  • CAS Number: 2308548-54-9
  • MF: C14H16N4O2S
  • MW: 304.37
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WR-1065

WR-1065 dihydrochloride can protect normal tissues from the toxic effects of certain cancer drugs and activate p53 through a JNK-dependent signaling pathway.

  • CAS Number: 14653-77-1
  • MF: C5H16Cl2N2S
  • MW: 207.16
  • Catalog: MDM-2/p53
  • Density: 0.975g/cm3
  • Boiling Point: 218.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 86ºC

Nutlin-3

(Rac)-Nutlin-3 (Rebemadlin), an active enantiomer of Nutlin-3, is a potent murine double minute (MDM2) inhibitor (IC50=90 nM). (Rac)-Nutlin-3 inhibits MDM2-p53 interactions and stabilizes the p53 protein, and induces cell autophagy and apoptosis. (Rac)-Nutlin-3 has the potential for the study of TP53 wild-type ovarian carcinomas[1][2].

  • CAS Number: 890090-75-2
  • MF: C30H30Cl2N4O4
  • MW: 581.49
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anticancer agent 50

Anticancer agent 50 (compound 6) is a potent ABCB1 efflux pump modulator. Anticancer agent 50 shows cytotoxic effects and antiproliferative effects. Anticancer agent 50 decreases the expression of cyclin D1 and induces p53 expression. Anticancer agent 50 has the potential for the research of T-lymphoma[1].

  • CAS Number: 2487457-15-6
  • MF: C30H32N2O4Se
  • MW: 563.55
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SLMP53-1

A novel reactivator of wild-type and mutant p53, shows a p53-dependent anti-proliferative activity in human wt and mut p53R280K-expressing tumor cells; enhances p53 transcriptional activity and restores wt-like DNA binding ability to mut p53R280K; inhibits the growth of wt/mut p53-expressing tumors in xenograft mice models, without apparent toxicity.

  • CAS Number: 1643469-17-3
  • MF: C20H18N2O2
  • MW: 318.376
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Condurango glycoside A

Condurango glycoside A is an activator of p53. Condurango glycoside A initiates ROS generation and up-regulates p53 expression. Condurango glycoside A induces apoptosis and pre-mature senescence associated with DNA damage in HeLa cells[1].

  • CAS Number: 11051-90-4
  • MF: C53H78O17
  • MW: 987.18
  • Catalog: Apoptosis
  • Density: 1.28±0.1 g/cm3(Predicted)
  • Boiling Point: 954.0±65.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

BAY 1892005

BAY 1892005 is a regulator of p53 protein and acts on p53 condensates without causing mutant p53 reactivation[1].

  • CAS Number: 2036352-13-1
  • MF: C11H8ClFN2OS
  • MW: 270.71
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPT2

CPT2 (Carnitine palmitoyltransferase 2), an enzyme that participates in fatty acid oxidation, also is a colorectal cancer (CRC) prognostic biomarker. CPT2 overexpression can activate p-p53 to increase p53 expression, thereby inhibiting tumor proliferation and promoting apoptosis. CPT2 deficiency results in the most common inherited disorder of long-chain fatty acid oxidation affecting skeletal muscle. Downregulation of CPT2 is also highly correlated with the progression of various cancers and has potential for cancer research[1][2].

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

Tenovin 6 Hydrochloride

Tenovin-6 Hydrochloride is a water soluble inhibitor of SIRT1 and SIRT2, slightly inhibits HDAC8, and is also a potent activator of p53, with IC50s of 21 μM, 10 μM, 67 μM for SirT1, SirT2, and SirT3, respectively.

  • CAS Number: 1011301-29-3
  • MF: C25H35ClN4O2S
  • MW: 491.089
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RO-5963

RO-5963 is a dual p53-MDM2 and p53-MDMX inhibitor with IC50s of ~17 nM and ~24 nM, respectively[1].

  • CAS Number: 1416663-77-8
  • MF: C24H21ClF2N4O5
  • MW: 518.90
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

APG-115

APG-115 (AA-115) is an orally active MDM2 protein inhibitor binding to MDM2 protein with IC50 and Ki values of 3.8 nM and 1 nM, respectively[1]. APG-115 blocks the interaction of MDM2 and p53 and induces cell-cycle arrest and apoptosis in a p53-dependent manner[2][3].

  • CAS Number: 1818393-16-6
  • MF: C34H38Cl2FN3O4
  • MW: 642.588
  • Catalog: MDM-2/p53
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 805.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 441.1±34.3 °C

Tenovin-3

Tenovin-3 is able to increase p53 levels, determined in MCF-7 cells treated for 6 hr at 10 μM.Target: p53in vitro: Tenovins inhibit the activities of human SirT1 and SirT2, two members of the NAD+-dependent class III histone deacetylases that also belong to the sirtuin family.[1]

  • CAS Number: 1011301-27-1
  • MF: C18H21N3OS
  • MW: 327.444
  • Catalog: MDM-2/p53
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sulanemadlin

Sulanemadlin (ALRN-6924) is a potent p53-based peptidomimetic macrocycles. Sulanemadlin is a inhibitor of the p53-MDM2, p53-MDMX, or both p53 and MDM2 and MDMX protein-protein interactions. Sulanemadlin can be used for cancers research[1].

  • CAS Number: 1451199-98-6
  • MF: C95H140N20O23
  • MW: 1930.25
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MA242

MA242 is a dual inhibitor of murine double minute 2 (MDM2) and nuclear factor of activated T cells 1 (NFAT1) for Pancreatic Cancer Therapy[1].

  • CAS Number: 1049704-18-8
  • MF: C26H21ClF3N3O5S
  • MW: 579.98
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MRT00033659

MRT00033659 is a potent broad-spectrum kinase inhibitor of CK1 (IC50=0.9 µM for CK1δ) and CHK1 (IC50=0.23 µM). MRT00033659, a pyrazolo-pyridine analogue, induces p53 pathway activation and E2F-1 destabilisation[1].

  • CAS Number: 1401731-54-1
  • MF: C15H14N4O
  • MW: 266.30
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MA242 free base

MA242 free base is a specific dual inhibitor of MDM2 and NFAT1. MA242 free base directly binds both MDM2 and NFAT1 with high affinity, induces their protein degradation, and inhibits NFAT1-mediated transcription of MDM2. MA242 free base induces apoptosis in pancreatic cancer cell lines regardless of p53 status[1].

  • CAS Number: 1049704-17-7
  • MF: C24H20ClN3O3S
  • MW: 465.95
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

c16 ceramide

C16-Ceramide is a natural small molecule activating p53 through the direct and selective binding[1].

  • CAS Number: 24696-26-2
  • MF: C34H67NO3
  • MW: 537.90100
  • Catalog: Apoptosis
  • Density: 0.919g/cm3
  • Boiling Point: 675.396ºC at 760 mmHg
  • Melting Point: 94-95ºC
  • Flash Point: 362.267ºC

ALRN-6924

ALRN-6924 is a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX[1].

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

NSC 207895

NSC-207895 (XI-006), a DNA damaging agent, is an anticancer agent and p53 activator[1][2][3].

  • CAS Number: 58131-57-0
  • MF: C11H13N5O4
  • MW: 279.252
  • Catalog: MDM-2/p53
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 487.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 248.7±31.5 °C

PK11007

PK11007 is a p53 targeting compound, has anti-tumor activities through activation of unstable p53.

  • CAS Number: 38275-34-2
  • MF: C6H5ClN2O4S
  • MW: 236.63300
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RDR03871

RDR03871 (compound 2) is a potent dual MDM2/MDM4 inhibitor with IC50 values of 35.4 nM and 10.4 nM for MDM2-p53 and MDM4-p53, respectively[1].

  • CAS Number: 286008-51-3
  • MF: C18H16ClF3N6
  • MW: 408.81
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

APR-246

PRIMA-1MET restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1MET also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.

  • CAS Number: 5291-32-7
  • MF: C10H17NO3
  • MW: 199.247
  • Catalog: MDM-2/p53
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 313.8±17.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 143.6±20.9 °C

UC2288

UC2288 is a novel, cell-permeable, and orally active p21 attenuator (relatively selective activity for p21), which is synthesized based Sorafenib (HY-10201). UC2288 decreases p21 mRNA expression independently of p53, and attenuates p21 protein levels with minimal effect on p21 protein stability. UC2288 has no inhibition of VEGFR2 and Raf kinases even at 10 μM[1].

  • CAS Number: 1394011-91-6
  • MF: C20H18ClF6N3O2
  • MW: 481.82
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-MORPHOLINOSYDNONIMINE

3-Morpholinosydnonimine (SIN-1; Linsidomine) is a spontaneous ROS/RNS generator and a peroxynitrite donor. 3-Morpholinosydnonimine inhibits hypertrophic chondrocytes activity and induces necrosis. 3-Morpholinosydnonimine induces p53-dependent apoptosis, induces p53 accumulation and activates MAPK phosphorylation[1][2].

  • CAS Number: 33876-97-0
  • MF: C6H10N4O2
  • MW: 170.16900
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRIMA-1

PRIMA-1 is a mutant p53 reactivator, restores the sensitivity of TP53 mutant-type thyroid cancer cells to the histone methylation inhibitor 3-Deazaneplanocin A.

  • CAS Number: 5608-24-2
  • MF: C9H15NO3
  • MW: 185.220
  • Catalog: MDM-2/p53
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 353.7±17.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 167.7±20.9 °C

Minocycline

Minocycline is an orally active, potent and BBB-penetrated semi-synthetic tetracycline antibiotic. Minocycline is a hypoxia-inducible factor (HIF)-1α inhibitor. Minocycline shows anti-cancer, anti-inflammatory, and glutamate antagonist effects. Minocycline reduces glutamate neurotransmission and shows neuroprotective properties and antidepressant effects. Minocycline inhibits bacterial protein synthesis through binding with the 30S subunit of the bacterial ribosome, resulting in a bacteriostatic effect[1][2][3][4][5][6][7].

  • CAS Number: 10118-90-8
  • MF: C23H27N3O7
  • MW: 457.476
  • Catalog: Bacterial
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 803.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 439.6±34.3 °C

Solasodine

Solasodine(Purapuridine) is a poisonous alkaloid chemical compound that occurs in plants of the Solanaceae family. Solasodine showed selective cytotoxicity against cervical cancer cell line (HeLa) and human myeloid leukemia cell line (U937).IC50 Value: 12.17 ± 3.3 uM (Hela cell line)[1]Target: Anticancerin vitro: Mouse embryonic teratocarcinoma P19 cells exposed to solasodine for 2 days followed by a 5-day washout differentiated into cholinergic neurons that expressed specific neuronal markers and displayed important axonal formation that continued growing even 30 days after treatment [2].in vivo: A 2-week infusion ofsolasodine into the left ventricle of the rat brain followed by a 3-week washout resulted in a significant increase in bromodeoxyuridine uptake by cells of the ependymal layer, subventricular zone, and cortex that co-localized with doublecortin immunostaining, demonstrating the proliferative and differentiating properties of solasodine on neuronal progenitors. Solasodine treatment in rats resulted in a dramatic increase in expression of the cholesterol- and drug-binding translocator protein in ependymal cells, suggesting a possible role played by neurosteroid production in solasodine-induced neurogenesis. In GAD65-GFP mice that express the green fluorescent protein under the control of the glutamic acid decarboxylase 65-kDa promoter, solasodine treatment increased the number of GABAergic progenitors and neuroblasts generated in the subventricular zone and present in the olfactory migratory tract [2]. intraperitoneal (i.p.) injection of solasodine (25 mg/kg) significantly delayed (p < 0.01) latency of hind limb tonic extensor (HLTE) phase in the PCT-induced convulsions. In the MES model, solasodine significantly reduced (p < 0.001) duration of HLTE at 25, 50, and 100 mg/kg, i.p. in a dose-dependent manner [3]. Oral administration (80 mg/kg body wt/day for 30 days) of solasodine (extracted and isolated from the berries of the Solanum xanthocarpum) to intact dogs significantly decreased the epithelial cell height of cauda epididymides [4].

  • CAS Number: 126-17-0
  • MF: C27H43NO2
  • MW: 413.636
  • Catalog: MDM-2/p53
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 537.9±50.0 °C at 760 mmHg
  • Melting Point: 284 °C (dec.)(lit.)
  • Flash Point: 279.1±30.1 °C

SP 141

SP-141 is a specific inhibitor of MDM2. SP-141 promotes MDM2 auto-ubiquitination and degradation. SP-141 might be used for the research of pancreatic cancer and breast cancer cells[1].

  • CAS Number: 1253491-42-7
  • MF: C22H16N2O
  • MW: 324.37500
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azurin p28 peptide

Azurin p28 peptide is a tumor-penetrated antitumor peptide. Azurin p28 peptide redues proteasomal degradation of p53 through formation of a p28: p53 complex. Azurin p28 peptide induces apoptosis or cell cycle arrest. Azurin p28 peptide inhibits p53-positive tumor growths. Azurin p28 peptide shows antiangiogenic effect by inhibiting phosphorylation of VEGFR-2, FAK and Akt[1][2][3].

  • CAS Number: 897026-25-4
  • MF: C122H197N31O47S2
  • MW: 2914.18
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A