다이너시크립
Dinaciclib![]() | |
임상 데이터 | |
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기타 이름 | SCH-727965 |
법적 상태 | |
법적 상태 |
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식별자 | |
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CAS 번호 | |
PubChem CID | |
IUPHAR/BPS | |
켐스파이더 | |
유니 | |
케그 | |
첸블 | |
PDB배위자 | |
CompTox 대시보드 (EPA ) | |
ECHA 정보 카드 | 100.246.885 |
화학 및 물리 데이터 | |
공식 | C21H28N6O2 |
몰 질량 | 396.495g/g−1/g |
3D 모델(JSmol) | |
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디나시클리브(SCH-727965)는 사이클린 의존성 키나아제(CDK)[1]를 억제하는 실험용 약물이다.다양한 암 [2]징후를 임상시험에서 평가하고 있다.
Dinaciclib은 Merck & Co.에 의해 개발되고 있다.그것은 [3]2011년 FDA로부터 고아 약물 지위를 부여받았다.
동작 메커니즘
- 사이클린 의존성 키나아제 억제제 디나시클리브는 [4]브로모도메인의 아세틸리신 인식 부위와 상호작용한다.
- Dinaciclib(SCH727665)는 CDK1 및 CDK5의존성 메커니즘을 [5]통해 전개단백질응답(UPR)을 억제한다.
항종양 작용
뉴런의 발달에 있어서의 역할
1차 배양 뉴런에서 dinaciclib은 상층 마커 Satb2의 발현을 감소시키는 신경 발생을 조절하고 더 깊은 [11]층의 뉴런에서 발현되는 CTIP2를 유도한다.
임상시험
- 단계 II
- 단계 III
- CLL[16] 치료를 위한 dinaciclib과 ofatumab의 비교
레퍼런스
- ^ Parry D, Guzi T, Shanahan F, Davis N, Prabhavalkar D, Wiswell D, Seghezzi W, Paruch K, Dwyer MP, Doll R, Nomeir A, Windsor W, Fischmann T, Wang Y, Oft M, Chen T, Kirschmeier P, Lees EM (Aug 2010). "Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor". Molecular Cancer Therapeutics. 9 (8): 2344–53. doi:10.1158/1535-7163.MCT-10-0324. PMID 20663931.
- ^ Bose P, Simmons GL, Grant S (Jun 2013). "Cyclin-dependent kinase inhibitor therapy for hematologic malignancies". Expert Opinion on Investigational Drugs. 22 (6): 723–38. doi:10.1517/13543784.2013.789859. PMC 4039040. PMID 23647051.
- ^ "Dinaciclib". AdisInsight. Retrieved 31 January 2017.
- ^ Martin MP, Olesen SH, Georg GI, Schönbrunn E (Nov 2013). "Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains". ACS Chemical Biology. 8 (11): 2360–5. doi:10.1021/cb4003283. PMC 3846258. PMID 24007471.
- ^ Nguyen TK, Grant S (Mar 2014). "Dinaciclib (SCH727965) inhibits the unfolded protein response through a CDK1- and 5-dependent mechanism". Molecular Cancer Therapeutics. 13 (3): 662–74. doi:10.1158/1535-7163.MCT-13-0714. PMC 3970263. PMID 24362465.
- ^ Desai BM, Villanueva J, Nguyen TT, Lioni M, Xiao M, Kong J, Krepler C, Vultur A, Flaherty KT, Nathanson KL, Smalley KS, Herlyn M (2013). "The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling". PLOS ONE. 8 (3): e59588. Bibcode:2013PLoSO...859588D. doi:10.1371/journal.pone.0059588. PMC 3601112. PMID 23527225.
- ^ Johnson AJ, Yeh YY, Smith LL, Wagner AJ, Hessler J, Gupta S, Flynn J, Jones J, Zhang X, Bannerji R, Grever MR, Byrd JC (Dec 2012). "The novel cyclin-dependent kinase inhibitor dinaciclib (SCH727965) promotes apoptosis and abrogates microenvironmental cytokine protection in chronic lymphocytic leukemia cells". Leukemia. 26 (12): 2554–7. doi:10.1038/leu.2012.144. PMC 3645353. PMID 22791353.
- ^ Feldmann G, Mishra A, Bisht S, Karikari C, Garrido-Laguna I, Rasheed Z, Ottenhof NA, Dadon T, Alvarez H, Fendrich V, Rajeshkumar NV, Matsui W, Brossart P, Hidalgo M, Bannerji R, Maitra A, Nelkin BD (Oct 2011). "Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models". Cancer Biology & Therapy. 12 (7): 598–609. doi:10.4161/cbt.12.7.16475. PMC 3218385. PMID 21768779.
- ^ Fu W, Ma L, Chu B, Wang X, Bui MM, Gemmer J, Altiok S, Pledger WJ (Jun 2011). "The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells". Molecular Cancer Therapeutics. 10 (6): 1018–27. doi:10.1158/1535-7163.MCT-11-0167. PMC 4727401. PMID 21490307.
- ^ Fu W, Sharma SS, Ma L, Chu B, Bui MM, Reed D, Pledger WJ (2013). "Apoptosis of osteosarcoma cultures by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a heat shock protein 90 inhibitor". Cell Death & Disease. 4 (3): e566. doi:10.1038/cddis.2013.101. PMC 3613821. PMID 23538447.
- ^ Ambrozkiewicz, Mateusz Cyryl; Bessa, Paraskevi; Salazar-Lázaro, Andrea; Salina, Valentina; Tarabykin, Victor (November 1, 2017). "Satb2Cre/+ mouse as a tool to investigate cell fate determination in the developing neocortex". Journal of Neuroscience Methods. 291: 113–121. doi:10.1016/j.jneumeth.2017.07.023. ISSN 1872-678X. PMID 28782628. S2CID 140208929.
- ^ Mita MM, Joy AA, Mita A, Sankhala K, Jou YM, Zhang D, Statkevich P, Zhu Y, Yao SL, Small K, Bannerji R, Shapiro CL (Jun 2014). "Randomized phase II trial of the cyclin-dependent kinase inhibitor dinaciclib (MK-7965) versus capecitabine in patients with advanced breast cancer". Clinical Breast Cancer. 14 (3): 169–76. doi:10.1016/j.clbc.2013.10.016. PMID 24393852.
- ^ Stephenson JJ, Nemunaitis J, Joy AA, Martin JC, Jou YM, Zhang D, Statkevich P, Yao SL, Zhu Y, Zhou H, Small K, Bannerji R, Edelman MJ (Feb 2014). "Randomized phase 2 study of the cyclin-dependent kinase inhibitor dinaciclib (MK-7965) versus erlotinib in patients with non-small cell lung cancer". Lung Cancer. 83 (2): 219–23. doi:10.1016/j.lungcan.2013.11.020. PMID 24388167.
- ^ "Phase II Trial of CDK Inhibitor Sch 727965 in Multiple Myeloma". 2 June 2014.
- ^ "A Phase II Trial of Sch 727965 (NSC 747135) in Patients with Stage IV Melanoma". 2 February 2022.
- ^ "A Phase 3 Study to Evaluate the Efficacy and Safety of Dinaciclib or Ofatumumab in Subjects with Refractory Chronic Lymphocytic Leukemia". 17 February 2017.
외부 링크
- 미국 국립 의학 도서관 의학 주제 제목(MeSH)의 dinaciclib