1160295-21-5
- Product Name：Pevonedistat Hcl
- Molecular Formula：C21H26ClN5O4S
- Purity：99%
- Molecular Weight：479.98
Product Details:
CasNo： 1160295-21-5
Molecular Formula： C21H26ClN5O4S
Appearance： White to off-white
Purity： 99%
Factory Supply High Purity Pevonedistat Hcl,Top Purity 99% 1160295-21-5 Efficient Shipping
Pevonedistat hydrochloride (MLN4924 hydrochloride) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor, with an IC50 of 4.7 nM[1].
Pevonedistat (MLN4924) is a potent inhibitor of NAE (half-maximal inhibitory concentration (IC50=0.004 μM), and is selective relative to the closely related enzymes UAE, SAE, UBA6 and ATG7 (IC50=1.5, 8.2, 1.8 and >10 μM, respectively). Pevonedistat (MLN4924) treatment inhibits overall protein turnover in cultured HCT-116 cells. Treatment of HCT-116 cells with Pevonedistat (MLN4924) for 24 h results in a dose-dependent decrease of Ubc12-NEDD8 thioester and NEDD8-cullin conjugates, with an IC50 < 0.1 μM, resulting in a reciprocal increase in the abundance of the known CRL substrates CDT1, p27 and NRF2 (also known as NFE2L2), but not non-CRL substrates[1]. Pevonedistat induces CLL cell apoptosis and circumvented stroma-mediated resistance. Pevonedistat promotes induction of Bim and Noxa in the CLL cells leading to rebalancing of Bcl-2 family members toward the proapoptotic BH3-only proteins[2]. Pevonedistat (MLN4924) rapidly inhibits cullin 1 neddylation and remarkably suppressed growth and survival as well as migration in a dose-and time-dependent manner in gastric cancer cells, and significantly suppresses migration by transcriptionally activating E-cadherin and repressing MMP-9[3].
Pevonedistat (MLN492410, 30 or 60 mg/kg, s.c.) leads to a dose- and time-dependent increase in the steady state levels of NRF2 and CDT1 in HCT-116 tumour-bearing mice, and decreases NEDD8-cullin levels in normal mouse tissue as illustrated in mouse bone marrow cells. Pevonedistat (MLN4924) administered on a BID schedule at 30 and 60 mg/kg inhibits tumour growth with T/C values of 0.36 and 0.15, respectively[1].
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03330106 | Millennium Pharmaceuticals, Inc.|Takeda |
Advanced Solid Neoplasm |
November 15, 2017 | Phase 1 |
| NCT03268954 | Takeda|Takeda Development Center Americas, Inc. |
Myelodysplastic Syndrome|Leukemia, Myelomonocytic, Chronic|Leukemia, Myeloid, Acute |
November 28, 2017 | Phase 3 |
| NCT02782468 | Millennium Pharmaceuticals, Inc.|Takeda |
Leukemia, Myeloid, Acute|Myelodysplastic Syndromes |
May 16, 2016 | Phase 1 |
| NCT03862157 | M.D. Anderson Cancer Center|National Cancer Institute (NCI) |
Acute Myeloid Leukemia|Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative|Chronic Eosinophilic Leukemia, Not Otherwise Specified|Chronic Myelomonocytic Leukemia|Chronic Neutrophilic Leukemia|Essential Thrombocythemia|Myelodysplastic Syndrome|Myelodysplastic+Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis|Myelodysplastic+Myeloproliferative Neoplasm, Unclassifiable|Myeloid Neoplasm|Myeloproliferative Neoplasm|Myeloproliferative Neoplasm, Unclassifiable|Overt Primary Myelofibrosis|Polycythemia Vera|Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase|Prefibrotic+Early Primary Myelofibrosis |
February 27, 2019 | Phase 1|Phase 2 |
| NCT03330821 | University of Southern California|National Cancer Institute (NCI) |
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome|Acute Myeloid Leukemia With Myelodysplasia-Related Changes|Therapy-Related Acute Myeloid Leukemia |
April 18, 2018 | Phase 1|Phase 2 |
| NCT03772925 | National Cancer Institute (NCI) |
Recurrent Acute Myeloid Leukemia|Recurrent Myelodysplastic Syndrome|Refractory Acute Myeloid Leukemia|Refractory Myelodysplastic Syndrome |
June 20, 2019 | Phase 1 |
| NCT03813147 | National Cancer Institute (NCI)|Children´s Oncology Group |
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome|Recurrent Acute Myeloid Leukemia|Recurrent Myelodysplastic Syndrome|Refractory Acute Myeloid Leukemia|Refractory Myelodysplastic Syndrome |
May 1, 2019 | Phase 1 |
| NCT00911066 | Millennium Pharmaceuticals, Inc. |
Acute Myelogenous Leukemia|Acute Lymphoblastic Leukemia|Myelodysplastic Syndrome |
June 2009 | Phase 1 |
| NCT01415765 | National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) |
Lymphoma, Diffuse Large-Cell B-cell|Diffuse, Large B-cell Lymphoma|Lymphoma, Diffuse Large-Cell|Large-Cell Lymphoma, Diffuse |
July 15, 2011 | Phase 1|Phase 2 |
| NCT03057366 | Millennium Pharmaceuticals, Inc.|Takeda |
Advanced Solid Tumors, Neoplasms, Advanced Solid |
May 11, 2017 | Phase 1 |
| NCT03386214 | Washington University School of Medicine|Takeda |
Myelofibroses |
April 23, 2018 | Phase 1 |
| NCT04712942 | University of Leipzig|Millennium Pharmaceuticals, Inc. |
Acute Myeloid Leukemia in Remission|Myelodysplastic Syndromes|Minimal Residual Disease |
January 1, 2021 | Phase 2 |
| NCT03745352 | National Cancer Institute (NCI) |
Recurrent Acute Myeloid Leukemia|Refractory Acute Myeloid Leukemia |
May 20, 2019 | Phase 2 |
| NCT02610777 | Millennium Pharmaceuticals, Inc.|Takeda |
Myelodysplastic Syndromes|Leukemia, Myelomonocytic, Chronic|Leukemia, Myeloid, Acute |
April 14, 2016 | Phase 2 |
| NCT04090736 | PETHEMA Foundation|Millennium Pharmaceuticals, Inc.|Dynamic Science S.L. |
Leukemia, Myeloid, Acute |
September 24, 2019 | Phase 3 |
| NCT04175912 | National Cancer Institute (NCI) |
Metastatic Cholangiocarcinoma|Metastatic Hepatocellular Carcinoma|Stage III Hepatocellular Carcinoma AJCC v8|Stage III Intrahepatic Cholangiocarcinoma AJCC v8|Stage IIIA Hepatocellular Carcinoma AJCC v8|Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8|Stage IIIB Hepatocellular Carcinoma AJCC v8|Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8|Stage IV Hepatocellular Carcinoma AJCC v8|Stage IV Intrahepatic Cholangiocarcinoma AJCC v8|Stage IVA Hepatocellular Carcinoma AJCC v8|Stage IVB Hepatocellular Carcinoma AJCC v8|Unresectable Cholangiocarcinoma|Unresectable Hepatocellular Carcinoma|Unresectable Intrahepatic Cholangiocarcinoma |
January 31, 2020 | Phase 2 |
| NCT03228186 | University of Michigan Rogel Cancer Center |
Non-small Cell Lung Cancer |
March 5, 2018 | Phase 2 |
| NCT03459859 | Justin Watts, MD|Takeda|University of Miami |
Acute Myelogenous Leukemia|AML|Advanced Myelodysplastic Syndromes|MDS |
May 21, 2018 | Phase 1 |
| NCT03814005 | Takeda |
Myelodysplastic Syndromes|Leukemia, Myelomonocytic, Chronic|Leukemia, Myeloid, Acute|Renal Insufficiency|Liver Disease|Neoplasms |
July 10, 2019 | Phase 1 |
| NCT04266795 | Takeda |
Acute Myeloid Leukemia (AML) |
October 13, 2020 | Phase 2 |
| NCT02122770 | Millennium Pharmaceuticals, Inc.|Takeda |
Advanced Solid Tumors |
April 1, 2014 | Phase 1 |
| NCT03013998 | Beat AML, LLC |
Previously Untreated Acute Myeloid Leukemia |
November 2016 | Phase 1|Phase 2 |
| NCT01862328 | Millennium Pharmaceuticals, Inc.|Takeda |
Solid Tumors |
June 10, 2013 | Phase 1 |
| NCT03709576 | Milton S. Hershey Medical Center|Millennium Pharmaceuticals, Inc.|Takeda |
Acute Myeloid Leukemia (AML) |
July 18, 2018 | Phase 2 |
| NCT03323034 | Children´s Oncology Group|National Cancer Institute (NCI) |
Recurrent Lymphoma|Recurrent Malignant Solid Neoplasm|Recurrent Primary Central Nervous System Neoplasm|Refractory Lymphoma|Refractory Malignant Solid Neoplasm|Refractory Primary Central Nervous System Neoplasm |
November 13, 2017 | Phase 1 |
| NCT04484363 | Takeda |
Myelodysplastic Syndromes |
||
| NCT03479268 | City of Hope Medical Center|National Cancer Institute (NCI) |
B-Cell Prolymphocytic Leukemia|Recurrent Chronic Lymphocytic Leukemia|Recurrent Diffuse Large B-Cell Lymphoma|Recurrent Follicular Lymphoma|Recurrent Lymphoplasmacytic Lymphoma|Recurrent Mantle Cell Lymphoma|Recurrent Marginal Zone Lymphoma|Recurrent Non-Hodgkin Lymphoma|Recurrent Small Lymphocytic Lymphoma|Refractory Chronic Lymphocytic Leukemia|Refractory Diffuse Large B-Cell Lymphoma|Refractory Follicular Lymphoma|Refractory Lymphoplasmacytic Lymphoma|Refractory Mantle Cell Lymphoma|Refractory Marginal Zone Lymphoma|Refractory Non-Hodgkin Lymphoma|Refractory Small Lymphocytic Lymphoma|Richter Syndrome |
March 22, 2018 | Phase 1 |
| NCT00677170 | Millennium Pharmaceuticals, Inc. |
Advanced Nonhematologic Malignancies |
April 2008 | Phase 1 |
| NCT04985656 | Takeda |
Myelodysplastic Syndromes (MDS) |
October 1, 2021 | Phase 2 |
| NCT03009240 | City of Hope Medical Center|National Cancer Institute (NCI) |
Acute Myeloid Leukemia|Recurrent Acute Myeloid Leukemia|Refractory Acute Myeloid Leukemia|Secondary Acute Myeloid Leukemia|Therapy-Related Acute Myeloid Leukemia|Untreated Adult Acute Myeloid Leukemia |
August 21, 2017 | Phase 1 |
| NCT03349281 | Julio Barredo, MD|Takeda|University of Miami |
Refractory Acute Lymphoblastic Leukemia|Relapsed Acute Lymphoblastic Leukemia |
March 25, 2019 | Phase 1 |
| NCT00722488 | Millennium Pharmaceuticals, Inc. |
Hematologic Malignancies|Multiple Myeloma|Lymphoma|Hodgkin Lymphoma |
June 2008 | Phase 1 |
| NCT03238248 | Vanderbilt-Ingram Cancer Center|National Cancer Institute (NCI) |
Myelodysplastic Syndromes|Myeloproliferative Neoplasm |
August 7, 2017 | Phase 2 |
| NCT03965689 | National Cancer Institute (NCI) |
Metastatic Lung Non-Small Cell Squamous Carcinoma|Metastatic Lung Non-Squamous Non-Small Cell Carcinoma|Stage IIIB Lung Cancer AJCC v8|Stage IV Lung Cancer AJCC v8|Stage IVA Lung Cancer AJCC v8|Stage IVB Lung Cancer AJCC v8|Unresectable Lung Non-Small Cell Carcinoma|Unresectable Lung Non-Squamous Non-Small Cell Carcinoma |
September 3, 2019 | Phase 2 |
| NCT01011530 | Millennium Pharmaceuticals, Inc. |
Metastatic Melanoma |
December 2009 | Phase 1 |
| NCT03319537 | Memorial Sloan Kettering Cancer Center|M.D. Anderson Cancer Center |
Mesothelioma |
October 5, 2017 | Phase 1|Phase 2 |
| NCT03770260 | National Cancer Institute (NCI) |
Recurrent Multiple Myeloma|Refractory Multiple Myeloma |
April 23, 2019 | Phase 1 |
| NCT04800627 | M.D. Anderson Cancer Center |
Locally Advanced Malignant Solid Neoplasm|Metastatic Malignant Solid Neoplasm|Unresectable Malignant Solid Neoplasm |
March 29, 2021 | Phase 1|Phase 2 |
| NCT03486314 | Millennium Pharmaceuticals, Inc.|Takeda |
Advanced Solid Neoplasm |
August 13, 2018 | Phase 1 |
| NCT01814826 | Millennium Pharmaceuticals, Inc.|Takeda |
Acute Myelogenous Leukemia |
April 10, 2013 | Phase 1 |
| NCT04172844 | Medical College of Wisconsin |
Acute Myelogenous Leukemia |
January 13, 2020 | Phase 1 |
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