DT2216

Bcl-xL-specific degrader

Also Known As:

(2S,4R)-1-((S)-2-(7-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-((trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)-7-oxoheptanamido)

Networked: 11 relevant articles (5 outcomes, 0 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Heterocyclic Compounds: 198
- 1-Ring Heterocyclic Compounds
  - Piperazines: 26
    - DT2216: 11

Experts

1.	Khan, Sajid: 4 articles (01/2022 - 12/2019)
2.	Thummuri, Dinesh: 4 articles (01/2022 - 12/2019)
3.	Zhang, Peiyi: 4 articles (01/2022 - 12/2019)
4.	Zheng, Guangrong: 4 articles (01/2022 - 12/2019)
5.	Zhou, Daohong: 4 articles (01/2022 - 12/2019)
6.	Budamagunta, Vivekananda: 3 articles (01/2022 - 01/2020)
7.	Zhang, Xuan: 3 articles (01/2022 - 12/2019)
8.	Hromas, Robert: 2 articles (01/2022 - 12/2019)
9.	Wiegand, Janet: 2 articles (01/2022 - 01/2022)
10.	He, Yonghan: 2 articles (01/2020 - 12/2019)

Related Diseases

1.	Neoplasms (Cancer) 01/01/2023 - "Only one cell line, SUP-T1, had significant resistance to DT2216, defined as an IC50 above what is achievable in murine tumors in vivo. " 12/01/2019 - "In vivo, DT2216 effectively inhibits the growth of several xenograft tumors as a single agent or in combination with other chemotherapeutic agents, without causing appreciable thrombocytopenia. " 01/01/2022 - "Furthermore, the therapeutic efficacy of sotorasib alone and in combination with DT2216 was evaluated in vivo using different tumor xenograft models. " 12/01/2019 - "We found that DT2216 was more potent against various BCL-XL-dependent leukemia and cancer cells but considerably less toxic to platelets than ABT263 in vitro because VHL is poorly expressed in platelets. " 01/01/2022 - "The combination of gemcitabine and DT2216 synergistically induced cell death in multiple pancreatic cancer cell lines in vitro In vivo, the combination significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice compared with the individual agents in pancreatic cancer PDX models. "
2.	Thrombocytopenia (Thrombopenia) 01/01/2020 - "In vivo, DT2216 alone was highly effective against MyLa TCL xenografts in mice without causing significant thrombocytopenia or other toxicity. " 12/01/2019 - "In vivo, DT2216 effectively inhibits the growth of several xenograft tumors as a single agent or in combination with other chemotherapeutic agents, without causing appreciable thrombocytopenia. " 01/01/2023 - "Indeed, DT2216 specifically degrades BCLXL via VHL E3 ligase, without inducing thrombocytopenia. " 01/01/2022 - "The combination of irinotecan and DT2216 in vitro on cells directly acquired from patients or in vivo using several xenografts derived from patients with FLC demonstrated remarkable synergy and at clinically achievable doses not associated with significant thrombocytopenia." 09/20/2023 - "While CG2 cells were rather resistant to BCL2 genetic knockdown or selective pharmacological inhibition with Venetoclax, they were vulnerable to strategies that target the megakaryocytic pro-survival factor BCL-XL (BCL2L1), including in vitro and in vivo treatment with BCL2/BCL-XL/BCL-W inhibitor Navitoclax and DT2216, a selective BCL-XL PROTAC (proteolysis-targeting chimera) degrader developed to limit thrombocytopenia in patients. "
3.	Pancreatic Neoplasms (Pancreatic Cancer) 01/01/2023 - "In addition, we recently demonstrated that the combination of sotorasib with DT2216 (a BCL-XL-selective degrader) synergistically inhibits G12C-mutated pancreatic cancer cell growth in vitro and in vivo. " 01/01/2022 - "Overcoming Gemcitabine Resistance in Pancreatic Cancer Using the BCL-XL-Specific Degrader DT2216." 01/01/2022 - "The combination of gemcitabine and DT2216 synergistically induced cell death in multiple pancreatic cancer cell lines in vitro In vivo, the combination significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice compared with the individual agents in pancreatic cancer PDX models. " 01/01/2022 - "We assessed the effect of sotorasib alone or in combination with DT2216 (a clinical-stage BCL-XL proteolysis targeting chimera [PROTAC]) on KRASG12C-mutated NSCLC, CRC and pancreatic cancer (PC) cell lines using MTS cell viability, colony formation and Annexin-V/PI apoptosis assays. " 01/01/2022 - "Pancreatic cancer cell dependencies on different BCL-2 family proteins and the efficacy of the combination of gemcitabine and DT2216 (a BCL-XL proteolysis targeting chimera or PROTAC) were determined by MTS, Annexin-V/PI, colony formation, and 3D tumor spheroid assays. "
4.	Leukemia 12/01/2019 - "We found that DT2216 was more potent against various BCL-XL-dependent leukemia and cancer cells but considerably less toxic to platelets than ABT263 in vitro because VHL is poorly expressed in platelets. "
5.	Drug-Related Side Effects and Adverse Reactions 01/01/2023 - "While targeting BCLXL using BH3 mimetics induces platelets on-target drug toxicity, the recent development of DT2216, a clinical-stage BCLXL proteolysis targeting chimera PROTAC compound, provides an alternative strategy to target BCLXL. "

Related Drugs and Biologics

1.	Proteolysis Targeting Chimera
2.	snake venom protein C activator
3.	navitoclax
4.	Annexin A5
5.	Proteins (Proteins, Gene)
6.	sotorasib
7.	Apoptosis Regulatory Proteins
8.	Gemcitabine
9.	(5- (2,4- bis((3S)- 3- methylmorpholin- 4- yl)pyrido(2,3- d)pyrimidin- 7- yl)- 2- methoxyphenyl)methanol
10.	Ubiquitin-Protein Ligases (Ubiquitin-Protein Ligase)

Related Therapies and Procedures

1.	Aftercare (After-Treatment)