Delving into the Latest Updates on Dinaciclib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Dinaciclib (USAN/INN), MK-7965, NSC-727135

+ [5]

Target

CDK1 x CDK2 x CDK5 x CDK9

Action

inhibitors

Mechanism

CDK1 inhibitors(Cyclin-dependent kinase 1 inhibitors), CDK2 inhibitors(Cyclin-dependent kinase 2 inhibitors), CDK5 inhibitors(Cyclin-dependent kinase 5 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication

Colorectal Liver MetastasesOsteosarcoma

Inactive Indication

Acute Lymphoblastic LeukemiaAcute Promyelocytic LeukemiaAdvanced breast cancer+ [15]

Originator Organization

Merck & Co., Inc.

Active Organization

Cincinnati Children's Hospital Medical Center

The Hebrew University of Jerusalem

Inactive Organization

Merck Sharp & Dohme Corp.Merck Sharp & Dohme LLC

AbbVie, Inc.

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

RegulationOrphan Drug (United States), Orphan Drug (European Union)

Login to view timeline

Structure/Sequence

Molecular FormulaC21H28N6O2

InChIKeyPIMQWRZWLQKKBJ-SFHVURJKSA-N

CAS Registry779353-01-4

The purpose of this trial is to determine the safety and tolerability (maximum tolerated dose (MTD)) of weekly dinaciclib in combination with pembrolizumab in patients with advanced breast cancer. Once this is defined, dose expansion will be performed at this MTD in patients with metastatic or locally advanced and unresectable triple negative breast cancer, to evaluate the efficacy of combined dinaciclib and pembrolizumab.

Start Date28 Dec 2016

Sponsor / Collaborator

The University of California, San Francisco

[+1]

NCT02684617

/ TerminatedPhase 1

Phase Ib Trial of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Subjects With Hematologic Malignancies (KEYNOTE-155).

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) used in combination with dinaciclib (MK-7965) in the treatment of relapsed or refractory chronic lymphocytic leukemia (rrCLL), multiple myeloma (rrMM), or diffuse large B-cell lymphoma (rrDLBCL).

Start Date29 Mar 2016

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with Dinaciclib

Login to view more data

100 Translational Medicine associated with Dinaciclib

Login to view more data

100 Patents (Medical) associated with Dinaciclib

Login to view more data

369

Literatures (Medical) associated with Dinaciclib

01 Mar 2026·EUROPEAN JOURNAL OF PHARMACOLOGY

Dinaciclib reduces MCL-1 levels and triggers apoptosis in adult T-cell leukemia/lymphoma

Article

Author: Kariya, Ryusho ; Sittithumcharee, Gunya ; Okada, Seiji ; Jirawatnotai, Siwanon

Adult T-cell leukemia/lymphoma (ATL) is a rare T-cell malignancy caused by long-term HTLV-1 infection. The disease is aggressive, with a median survival of 8-10 months, and no new treatments are currently available. Dinaciclib is a selective small-molecule drug that targets CDK1, CDK2, CDK5, and CDK9. This study assessed dinaciclib's ability to inhibit ATL cells. It significantly suppressed ATL proliferation at low nanomolar concentrations. The antiproliferative effect was due to induced apoptotic cell death, as shown by FACS analysis. Annexin/PI staining revealed morphological signs of apoptosis after dinaciclib treatment, while pre-treatment with Q-VD-OPh prevented apoptosis in ATL cells. The primary mechanism by which dinaciclib induces apoptosis appears to involve deregulation of anti-apoptotic proteins, especially MCL-1. MCL-1 protein levels decreased significantly in a dose- and time-dependent manner, coinciding with caspase-3 activation. The anti-tumor effects of dinaciclib were confirmed in an in vivo xenograft model. Overall, this study demonstrates that dinaciclib effectively targets ATL cells by inducing MCL-1 deregulation and promoting apoptotic cell death.

01 Mar 2026·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Unveiling the mechanistic link between peroxiredoxin inhibition and ferroptosis-like cell death induced by Dinaciclib in Entamoeba histolytica

Article

Author: Feng, Meng ; Dong, Dai ; Cheng, Xunjia ; Zhou, Ruixue ; Li, Wenjie ; Zhang, Hongze

Entamoeba histolytica lacks a canonical glutathione-based antioxidant system and primarily relies on the thioredoxin pathway for redox homeostasis, making peroxiredoxin (EhPrx) a critical vulnerability and potential therapeutic target. Through structure-based screening, Dinaciclib was identified as a novel direct inhibitor of EhPrx. Pharmacological targeting of EhPrx by Dinaciclib triggers a ferroptosis-like cell death pathway characterized by oxidative stress and significant accumulation of intracellular iron and lipid peroxides. In contrast, the well-established ferroptosis inducer RSL3 did not induce lipid peroxidation but instead upregulated EhPrx expression, suggesting an adaptive defense mechanism against indirect oxidative stress. Transcriptomic analysis following Dinaciclib treatment revealed widespread dysregulation of genes central to ferroptosis, including those involved in iron, lipid, and cysteine metabolism. Collectively, our results suggest that targeting EhPrx overwhelms the parasite's primary redox defense, leading to iron-driven oxidative cell death. Thus, this study identifies EhPrx as an exploitable target and proposes a distinct mechanism that triggers ferroptosis-like death in E. histolytica.

01 Jan 2026·BIOORGANIC CHEMISTRY

Design, synthesis and molecular docking of Pyrazolo[3,4-b]pyridine derivatives as potential CDK2 pathway inhibitors in colorectal cancer cells

Article

Author: Nasr, Jamal ; Kassem, Zahra A ; Merhi, Raghida Abou ; Youssef, Ali ; Darwiche, Nadine ; Staiteieh, Soumaiah Abou ; Issa, Doaa A E

Within the framework of discovering novel colorectal cancer chemotherapeutic agents with improved efficacy and safety profiles, efforts were directed towards advancing this area of research. In this study, new pyrazolo[3,4-b]pyridine series were designed as Cyclin Dependent Kinase 2 (CDK2) inhibitors, synthesized, and biologically evaluated. All chemical structures were docked into the active site of CDK2 crystalline structure (1HCK). Binding energies and receptor interactions were elucidated. Antiproliferative activities against human colorectal cancer (CRC) cell lines HCT-116, HT-29 and related cytotoxicity on non-tumorigenic human colorectal cell line NCM-460D were studied by MTT assays. Compounds 6, 9c, 10, and 14 possessed notable activity against HCT-116 and HT-29 cells with IC₅₀ values ranging from 11.11 to 62.61 μM. Compounds 6, 10, and 14 exhibited low cytotoxicity on NCM-460D, promoting them as promising chemotherapeutic agents. Structure-Activity Relationship of synthesized compounds was established, highlighting the influence of extended planarity, aromatic environments, and presence of electron donor-acceptor groups. Compounds 6 and 14 were selected for molecular investigations. They were not considered pro-apoptotic and showed non-significant influence on CDK2 protein expression. However, they displayed a dose-dependent inhibition of CDK2 kinase activity in in-vitro ADP-Glo™ assay with IC₅₀ values of 23.47 and 82.04 nM, respectively, compared to 0.51 and 700 nM for Dinaciclib and Roscovitine, respectively. Compound 6 downregulated CDK2 protein targets involved in DNA replication process; Polα, MCM7, ORC2, and ORC4 in CRC cell lines. Subjected to cell cycle analysis, HCT-116 and HT-29 treated with compound 6 demonstrated pre-G1 phase arrest with no similar observation in S phase.

2

News (Medical) associated with Dinaciclib

11 Apr 2024

·www.sciencedaily.com

Scientists uncover key resistance mechanism to Wnt inhibitors in pancreatic and colorectal cancers

A new study reveals why some pancreatic and colorectal tumors resist targeted anti-Wnt drugs and suggests how to overcome it, offering new hope to patients with fully treatment-resistant cancers. Scientists at Duke-NUS Medical School have uncovered why some pancreatic and colorectal cancers[1] fail to respond to Wnt inhibitors, a promising new class of cancer drugs currently under development for these cancers. Their discovery, published in Science Advances, not only offers a new cancer therapy target but also a potential screening tool to identify those patients who will not benefit from this new therapy once it becomes available. Many gastrointestinal cancers grow uncontrollably when a mutation sets a key biological pathway that governs cell growth, called Wnt, on hyperdrive. The Wnt pathway is hijacked in this way in more than 80 per cent of colorectal cancers and some pancreatic cancers, driving rampant tumour growth. For this group of patients, drugs that block the Wnt pathway, known as Wnt inhibitors, hold great promise and they have been at the centre of intense scientific study, including at Duke-NUS[2]. "Although Wnt inhibitors have shown some promise in certain patients, our study reveals intrinsic resistance in others," said Dr Zhong Zheng, who led the study as a postdoctoral fellow at Duke-NUS' Cancer & Stem Cell Biology Programme. "Understanding the mechanisms behind this resistance is crucial for personalised treatments for patients when the drugs don't slow tumour growth at all." Focusing on colorectal and pancreatic cancers with a hyperactive Wnt pathway, Dr Zhong, together with Professor David Virshup who leads the Programme at Duke-NUS, used their Wnt inhibiting drug ETC-159, whose efficacy had been established in preclinical models, to assess the cancer cells' responsiveness. By analysing genetics data on both responsive and non-responsive tumours, they discovered that a second mutation in another gene, known as FBXW7, makes cancer cells stubbornly resistant to Wnt-blocking drugs. FBXW7 mutations occur in about 15 per cent of colorectal cancers. "The FBXW7 mutations change the personality of the cancer," explained Dr Zhong. "They no longer 'care' about the Wnt pathway and so the drugs no longer can do their work." Testing tumours for the FBXW7 genetic mutations could spare many patients from receiving ineffective treatment, making this not only a potential biomarker but also as a target for a new type of cancer treatment. "Predicting drug resistance is critical for precision oncology," said senior author Prof Virshup. "This work reveals how cancers can evade dependencies on Wnt signalling and serves as a solid foundation for further development." "We can now try to target those backup pathways activated by the FBXW7 mutation to overcome the drug resistance," added Dr Zhong, pointing to new treatment possibilities. The findings add to previous work by the scientists on how pancreatic cancers become resistant to treatment. Together, these discoveries increase our understanding of the ways cancers find alternate routes to grow and survive. With more precise therapeutic targets to lock onto, these findings bring the promise of personalised therapies one step closer to reality. In addition to the discovery of FBXW7, the team found these Wnt inhibitor-resistant tumours to be susceptible to an experimental drug known as dinaciclib. Their next step is to investigate the potential of dinaciclib alone and in combination with other agents in treating these cancers. "Our ultimate goal is to help patients with fully resistant tumours by targeting the alternate cancer pathways unleashed by FBXW7 mutations," said Prof Virshup. "We hope to translate our findings into more tailored and potent treatment strategies." "This research exemplifies the highly translational nature of the basic scientific research conducted at Duke-NUS. Cancers are notoriously diverse, and it is important that we can understand and map that diversity, so that we can offer truly personalised treatment that is effective for the individual and not leave patients to undergo unnecessary therapies that will not work for them," said Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS. "This study is another important step on our journey to make every cancer a treatable disease and the team's exemplifies our resolve to deliver more effective therapies to patients." [1] Colorectal cancers are the second most common type of cancer diagnosed in Singapore for both men and women. Pancreatic cancer is the 10th most common cause of cancer in men in Singapore. The World Health Organisation estimated that in 2020 alone, more than 1.9 million new cases of colorectal cancers were diagnosed worldwide. [2] Duke-NUS, together with A*STAR, developed a made-in-Singapore Wnt inhibitor called ETC-159 which is currently in early phase clinical trials.

15 Sep 2023

·synapse.patsnap.com

CDK2 Inhibitor——Important Regulator of Cell Cycle Control

Cyclin-dependent kinases (CDKs), a serine/threonine family kinase, play a key role in cell cycle regulation and transcriptional activity. The activity of CDKs depends on their associated Cyclin subunits and non-catalytic regulatory proteins, which form CDK-Cyclin heterodimer complexes, playing a crucial role in regulating different biological processes. These processes include angiogenesis, hematopoiesis, gene transcription, apoptosis, neuronal activity, metabolism, DNA repair, exocytosis, and spermatogenesis. To date, at least nine types of CDKs have been identified in humans, labeled as CDK1-CDK9. In different tumor cells, cell cycle dysregulation often accompanies changes in CDK activity and/or its interacting proteins. Hence, the development of novel CDK inhibitors becomes an effective approach to combat various malignancies. CDK2, or cyclin-dependent kinase 2, is a crucial protein involved in cell cycle regulation in the human body. It plays a pivotal role in controlling the progression of cells from the G1 phase to the S phase, allowing DNA replication and cell division to occur. CDK2 forms complexes with cyclins, which activate its kinase activity, leading to the phosphorylation of various target proteins involved in cell cycle progression. Dysregulation of CDK2 activity has been implicated in numerous diseases, including cancer, making it an attractive target for therapeutic interventions aimed at controlling cell proliferation and promoting healthy cell cycle progression. CDK2 Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 10 Sep 2023, there are a total of 64 CDK2 drugs worldwide, from 72 organizations, covering 69 indications, and conducting 75 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of the target CDK2 reveals that Merck KGaA, Pfizer Inc., and Cyclacel Pharmaceuticals, Inc. are the companies with the highest stage of development. The drugs under the target CDK2 have been approved for indications such as B-Cell Chronic Lymphocytic Leukemia, Non-Small Cell Lung Cancer, Ovarian Cancer, and Triple Negative Breast Cancer. Small molecule drugs are progressing most rapidly, indicating intense competition in the market. The United States, European Union, and several other countries are actively developing drugs targeting CDK2. Overall, the target CDK2 shows a competitive landscape with potential for future development in various indications and drug types. The multi-target CDK2 inhibitor Dinaciclib enters phase III clinical trialsDinaciclib is a small molecule drug that targets multiple CDKs, including CDK1, CDK2, CDK5, and CDK9. It is being developed by Merck & Co., Inc. and is currently in Phase 3, which is the final stage of clinical trials before seeking regulatory approval. The drug has shown potential therapeutic benefits in the treatment of neoplasms, immune system diseases, and hemic and lymphatic diseases. Specifically, it has demonstrated efficacy in B-cell chronic lymphocytic leukemia (B-CLL) and acute myeloid leukemia (AML). These indications are characterized by the abnormal growth and proliferation of certain cells in the blood and bone marrow. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Dinaciclib's mechanism of action involves inhibiting CDKs, which are enzymes involved in cell cycle regulation and transcriptional control. By targeting multiple CDKs, the drug aims to disrupt the abnormal cell growth and division observed in cancer and other diseases. One notable aspect of Dinaciclib is its orphan drug status. Orphan drugs are medications developed to treat rare diseases or conditions that affect a small number of patients. This designation provides certain incentives and benefits to the drug developer, such as extended market exclusivity and financial support for clinical trials. Overall, Dinaciclib holds promise as a potential treatment option for B-CLL and AML, two types of leukemia. Its small molecule nature and ability to target multiple CDKs make it an interesting candidate for further development. The ongoing Phase 3 trials will provide crucial data on its safety and efficacy, which will determine its potential for regulatory approval and commercialization. Selective CDK2 inhibitor PF-07104091 enters Phase II clinical trialThe drug PF-07104091 is a small molecule drug that targets CDK2, a protein involved in cell cycle regulation. It is being developed by Pfizer Inc., a leading pharmaceutical company. PF-07104091 has shown potential in treating various therapeutic areas, including neoplasms (abnormal growth of cells), skin and musculoskeletal diseases, endocrinology and metabolic diseases, respiratory diseases, and urogenital diseases. It is specifically indicated for non-small cell lung cancer, ovarian cancer, small cell lung cancer, triple negative breast cancer, solid tumors, breast cancer, and hormone receptor positive HER2 negative breast cancer. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Currently, PF-07104091 has reached Phase 2 of clinical development globally. In China, it has reached Phase 1/2, indicating that it is still in the early stages of development in this region. The objective presentation of this information allows stakeholders in the pharmaceutical industry to understand the key details of PF-07104091. The drug's small molecule nature suggests that it may have advantages in terms of formulation and delivery. Its target, CDK2, is a well-known protein involved in cell cycle regulation, making it a promising target for therapeutic intervention. The wide range of therapeutic areas and indications for PF-07104091 indicates its potential for treating various diseases. Non-small cell lung cancer, ovarian cancer, and breast cancer are among the most prevalent and challenging cancers globally, making the drug's potential impact significant. The fact that PF-07104091 has reached Phase 2 globally suggests that it has shown promising results in early clinical trials, demonstrating its safety and efficacy to a certain extent. However, its current phase in China, Phase 1/2, indicates that further research and development are needed to establish its effectiveness in this specific market. In summary, PF-07104091 is a small molecule drug developed by Pfizer Inc. that targets CDK2. It has shown potential in treating various therapeutic areas and indications, particularly in the field of oncology. While it has reached Phase 2 globally, further development is required in China. This objective summary provides a concise overview of the drug's key details, allowing stakeholders to assess its potential and make informed decisions.

100 Deals associated with Dinaciclib

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D09604	Dinaciclib	-	DB12021

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic lymphocytic leukaemia refractory	Phase 3	-	Merck Sharp & Dohme Corp.	01 Aug 2012
B-Cell Leukemia	Phase 2	-	Merck Sharp & Dohme Corp.	01 Mar 2009
B-Cell Lymphoma	Phase 2	-	Merck Sharp & Dohme Corp.	01 Mar 2009
Mantle cell lymphoma refractory	Phase 2	-	Merck Sharp & Dohme Corp.	01 Mar 2009
Acute Lymphoblastic Leukemia	Phase 2	-	Merck Sharp & Dohme Corp.	01 Jan 2009
Acute Promyelocytic Leukemia	Phase 2	-	Merck Sharp & Dohme Corp.	01 Jan 2009
CD33-positive Acute Myeloid Leukemia	Phase 2	-	Merck Sharp & Dohme Corp.	01 Jan 2009
Breast Cancer	Phase 2	-	Merck Sharp & Dohme Corp.	01 Jul 2008
Non-Small Cell Lung Cancer	Phase 2	-	Merck Sharp & Dohme Corp.	01 Jul 2008
Refractory acute myeloid leukemia	Phase 1	United States	AbbVie, Inc.	23 Jul 2018

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00937937 (Southwest Oncology Group S0826, Pubmed \| Cancer) Manual	Phase 2	Melanoma	72	SCH 727965 50 mg/m2	vdvudhxyty(asqnsarwld) = hxlnhtdpht imtseowmqy (eqyihodmun, 5.5 - 10.5) View more	Negative	01 Jan 2025
NCT02684617 (KEYNOTE-155, CTgov)	Phase 1	Chronic Lymphocytic Leukemia \| Recurrent Chronic Lymphoid Leukemia \| Multiple Myeloma ... View more	75	dinaciclib+pembrolizumab (rrCLL Cohort)	aellziwerg = ijgsfdkrbd sofwkezeey (jooyitwale, mzjeygcpmj - zugsyfmecz) View more	-	01 Mar 2021
NCT02684617 (KEYNOTE-155, CTgov)	Phase 1		75	dinaciclib+pembrolizumab (rrMM Cohort)	aellziwerg = wyzzcyrnmh sofwkezeey (jooyitwale, ekqwufkaga - uqlzxpurlu) View more	-	01 Mar 2021
NCT01783171 (Pubmed \| Clin Transl Sci) Manual	Phase 1	Pancreatic Cancer	39	MK-2206+Dinaciclib	ztgqvwdqlm(xhibiutttw) = dinaciclib 9 mg/m2 and MK-2206 135 mg tvwbrmstek (mfzpmonkds ) View more	Negative	01 Nov 2020
NCT01676753 (ASCO 12020 \| ASCO 22020) Manual	Phase 1	Triple Negative Breast Cancer HER2 Negative \| ER Negative \| PR Negative	32	dinaciclib+pembrolizumab	vrsbcwygzy(tsanjxustn) = The RP2D of dina given in combination with standard dose P is 33 mg/m2 frosfhtyat (mnogpwinfl ) View more	Positive	29 May 2020
NCT01676753 (ASCO2019)	Phase 1	Triple Negative Breast Cancer	22	Dinaciclib + Pembrolizumab	itedhvonlo(jatvewumdl) = ijxbwefvcy yzyvuaqzgf (hhyhloalgy ) View more	-	26 May 2019
NCT01515176 (CTgov)	Phase 1/2	Chronic lymphocytic leukaemia refractory \| B-Cell Prolymphocytic Leukemia \| Small Lymphocytic Lymphoma	36	Pharmacological Study+Dinaciclib+Ofatumumab	zsyqtzqivu = blufospcxo bhkeogsrdv (scgwapzpgr, xzsqusnjey - ziiafnfglf) View more	-	15 Mar 2018
NCT00871910 (P04630, Pubmed \| Med J Aust \| Br J Cancer) Manual	Phase 1	Neoplasms	61	dinaciclib	aohhicixcs(yklpssjkey) = pancytopenia, neutropenic fever, elevated transaminases, hyperuricemia and hypotension nxvzhohmpr (yixttvjboc ) View more	Positive	24 Oct 2017
AACR2017	Phase 1	Advanced Malignant Solid Neoplasm	-	Dinaciclib + Veliparib	zeolzvnodj(krviwulxxh) = iwiuhygmrh vmbmhakzbb (ncthnqkwio )	-	01 Jul 2017
NCT01026324 (CTgov)	Phase 1/2	Melanoma \| Unresectable Melanoma	12	Dinaciclib (Treatment (Dinaciclib) Dose Level 1)	xivfinontp = rhwxhnkatz visqgzmarg (weyrqrnhpr, jplwfnifyu - rpitstqvaw) View more	-	03 Aug 2016
NCT01026324 (CTgov)	Phase 1/2	Melanoma \| Unresectable Melanoma	12	Dinaciclib (Treatment (Dinaciclib) Dose Level 2)	xivfinontp = qolomsqrrm visqgzmarg (weyrqrnhpr, ypseesmmqp - yicvsilfhb) View more	-	03 Aug 2016
NCT00937937 (Southwest Oncology Group S0826, CTgov)	Phase 2	Mucosal Melanoma \| Acral Lentiginous Malignant Melanoma \| Melanoma recurrent	72	dinaciclib (Dinaciclib)	razshyfnkc(eznoimqciz) = ogrobcpsyp nhkkexdeqi (wjzmzjhymf, jbzcwisumf - eegxqrpzhr) View more	-	22 Jul 2016
NCT00937937 (Southwest Oncology Group S0826, CTgov)	Phase 2		72	SCH 727965 (SCH 727965)	opxjerknrn(szbpchugwg) = watnxfzvoa ftmzdrsyhg (jbvgwyvurr, pautnyjjra - ibigmlbala) View more	-	22 Jul 2016