Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C30H30Cl2N4O4 |
| Molecular Weight | 581.49 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=C(C2=N[C@@H]([C@@H](N2C(=O)N3CCNC(=O)C3)C4=CC=C(Cl)C=C4)C5=CC=C(Cl)C=C5)C(OC(C)C)=C1
InChI
InChIKey=BDUHCSBCVGXTJM-IZLXSDGUSA-N
InChI=1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13,16,18,27-28H,14-15,17H2,1-3H3,(H,33,37)/t27-,28+/m1/s1
| Molecular Formula | C30H30Cl2N4O4 |
| Molecular Weight | 581.49 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22995624
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22995624
Nutlin-3b is pharmacologically inactive enantiomer of an Mdm2 (mouse double minute 2) antagonist and apoptosis inducer nutlin-3. Nutlin-3b binds to MDM2 with 200-fold lower affinity and is 150 times less active in vitro than 3a (an active enantiomer of nutlin-3). Nutlin-3b does not show any effect on the cell cycle and proliferation and has no insignificant effect on gene expression in cancer cells. Nutlin-3b is usually used as a negative control.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Therapeutic potential of Mdm2 inhibition in malignant germ cell tumours. | 2010-04 |
|
| DNA damage response to the Mdm2 inhibitor nutlin-3. | 2010-02-15 |
|
| The expression levels of the pro-apoptotic XAF-1 gene modulate the cytotoxic response to Nutlin-3 in B chronic lymphocytic leukemia. | 2010-02 |
|
| Nutlin-3 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulation of death receptor 5 (DR5) in human sarcoma HOS cells and human colon cancer HCT116 cells. | 2010-01-01 |
|
| Selective FLT3 inhibitor FI-700 neutralizes Mcl-1 and enhances p53-mediated apoptosis in AML cells with activating mutations of FLT3 through Mcl-1/Noxa axis. | 2010-01 |
|
| Interactions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib. | 2009-12-01 |
|
| Suppression of hypoxia-inducible factor 2alpha restores p53 activity via Hdm2 and reverses chemoresistance of renal carcinoma cells. | 2009-12-01 |
|
| High level MycN expression in non-MYCN amplified neuroblastoma is induced by the combination treatment nutlin-3 and doxorubicin and enhances chemosensitivity. | 2009-12 |
|
| Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53. | 2009-11-18 |
|
| Oncogenic RAS enables DNA damage- and p53-dependent differentiation of acute myeloid leukemia cells in response to chemotherapy. | 2009-11-05 |
|
| Nutlin-3, an Hdm2 antagonist, inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated inactivation of HIF-1alpha. | 2009-10 |
|
| Nutlin-3 affects expression and function of retinoblastoma protein: role of retinoblastoma protein in cellular response to nutlin-3. | 2009-09-25 |
|
| MI-63: a novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53. | 2009-09-01 |
|
| Specific activation of the p53 pathway by low dose actinomycin D: a new route to p53 based cyclotherapy. | 2009-09-01 |
|
| Activation of p53 by MDM2 antagonists has differential apoptotic effects on Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt's lymphoma cells. | 2009-09 |
|
| Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance. | 2009-08-28 |
|
| HIPK2 regulation by MDM2 determines tumor cell response to the p53-reactivating drugs nutlin-3 and RITA. | 2009-08-01 |
|
| The emerging molecular pathogenesis of neuroblastoma: implications for improved risk assessment and targeted therapy. | 2009-07-27 |
|
| Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. | 2009-07 |
|
| Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cells. | 2009-06-15 |
|
| Exposure of B cell chronic lymphocytic leukemia (B-CLL) cells to nutlin-3 induces a characteristic gene expression profile, which correlates with nutlin-3-mediated cytotoxicity. | 2009-06 |
|
| Cyclin-dependent kinase 1 inhibitor RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis in AML. | 2009-06 |
|
| Expression of Epstein-Barr virus BZLF1 immediate-early protein induces p53 degradation independent of MDM2, leading to repression of p53-mediated transcription. | 2009-05-25 |
|
| The MDM2 antagonist nutlin-3 sensitizes p53-null neuroblastoma cells to doxorubicin via E2F1 and TAp73. | 2009-05 |
|
| Nutlin-3 up-regulates the expression of Notch1 in both myeloid and lymphoid leukemic cells, as part of a negative feedback antiapoptotic mechanism. | 2009-04-30 |
|
| Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway. | 2009-04-02 |
|
| Role of polyamines in p53-dependent apoptosis of intestinal epithelial cells. | 2009-04 |
|
| Reactivation of p53 function in synovial sarcoma cells by inhibition of p53-HDM2 interaction. | 2009-03-18 |
|
| p53 Deficiency leads to compensatory up-regulation of p16INK4a. | 2009-03 |
|
| RNA interference screening demystified. | 2009-03 |
|
| Hdm2 is regulated by K-Ras and mediates p53-independent functions in pancreatic cancer cells. | 2009-02-05 |
|
| Survival-related profile, pathways, and transcription factors in ovarian cancer. | 2009-02-03 |
|
| MDM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma. | 2009-02-01 |
|
| Reversal of P-glycoprotein-mediated multidrug resistance by the murine double minute 2 antagonist nutlin-3. | 2009-01-15 |
|
| Establishment of a dog model for the p53 family pathway and identification of a novel isoform of p21 cyclin-dependent kinase inhibitor. | 2009-01 |
|
| P53 family: at the crossroads in cancer therapy. | 2009 |
|
| A large scale shRNA barcode screen identifies the circadian clock component ARNTL as putative regulator of the p53 tumor suppressor pathway. | 2009 |
|
| The proliferative human monocyte subpopulation contains osteoclast precursors. | 2009 |
|
| Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy. | 2009 |
|
| SUMO-specific protease 2 is essential for modulating p53-Mdm2 in development of trophoblast stem cell niches and lineages. | 2008-12-16 |
|
| Syntaxin 6, a regulator of the protein trafficking machinery and a target of the p53 family, is required for cell adhesion and survival. | 2008-11-07 |
|
| RHAMM is differentially expressed in the cell cycle and downregulated by the tumor suppressor p53. | 2008-11-01 |
|
| Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas. | 2008-10-13 |
|
| Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia. | 2008-10-01 |
|
| Multiple p53-independent gene silencing mechanisms define the cellular response to p53 activation. | 2008-08 |
|
| Mdm2 and Mdm4 loss regulates distinct p53 activities. | 2008-06 |
|
| Comparisons of robustness and sensitivity between cancer and normal cells by microarray data. | 2008 |
|
| p53-Repressed miRNAs are involved with E2F in a feed-forward loop promoting proliferation. | 2008 |
|
| p53 plays a role in mesenchymal differentiation programs, in a cell fate dependent manner. | 2008 |
|
| Disruption of the p53-Mdm2 complex by Nutlin-3 reveals different cancer cell phenotypes. | 2008 |
Sample Use Guides
Nude mice (10 animals per dose group) bearing subcutaneous human cancer xenografts (SJSA-1) with mean volumes of 185 mm3 received 200 mg/kg of an oral dose of Nutlin-3 (racemic) twice daily
Route of Administration:
Oral
Effect of the enantiomers of Nutlin-3 on the growth and viability of cancer cells were evaluated in cell lines with wild-type p53 (HCT116, RKO, and SJSA-1) and mutant p53 (MDA-MB-435 and SW480). Cells were incubated with 10 mkM enantiomer-a or -b (Nutlin-3b) for 24 and 48 hours, and the TUNEL-positive cell fractions were measured by flow cytometry
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 22:04:22 GMT 2025
by
admin
on
Mon Mar 31 22:04:22 GMT 2025
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| Record UNII |
FJA1772CVW
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| Record Status |
Validated (UNII)
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| Record Version |
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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RACEMATE -> ENANTIOMER |
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