ReviewBiochemical pharmacology2026
Saga of MCL1 inhibitors in multiple myeloma.
Review in Biochemical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02675452 (A Phase 1 First in Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 176 in Subjects With Relapsed or Refractory Multiple Myeloma and Subjects With Relapsed or Refractory Acute Myeloid Leukemia), which is not on this map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 First in Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 176 in Subjects With Relapsed or Refractory Multiple Myeloma and Subjects With Relapsed or Refractory Acute Myeloid Leukemia
Who cites it
1 citing paper in PubMed.
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Myeloid cell leukemia 1 (MCL1) is an anti-apoptotic protein within the B-cell lymphoma 2(Bcl-2) family that is aberrantly overexpressed in many cancers such as Multiple Myeloma (MM). The protein is a key contributor to MM relapses, and effectively inhibiting MCL1 is a solution to overcoming drug resistance. Since MCL1 was identified in 1993, significant progress has been made in investigating the protein's role in cancer development and the benefits of inhibition. After years of research, in 2008 AbbVie developed the first small molecule inhibitor, A-1210477, with an indole-2-carboxylic acid core that targeted MCL1's BH3 binding groove selectively and had low affinity for Bcl-2 and Bcl-xL. Following this, there was a surge in the development of novel MCL1 inhibitors, which are still being produced today. In 2016, the first MCL1 SMI, AMG 176, advanced to a phase 1 clinical trial for relapsed/refractory (R/R) MM patients and was sponsored by Amgen (NCT02675452). Spanning 8 years, this trial is the longest to date among all studies investigating MCL1 inhibition in patients with R/R MM. Six novel MCL1 inhibitors have been evaluated in clinical trials for R/R MM patients, sponsored by six different pharmaceutical companies. Adverse side effects and particularly cardiotoxicity present a significant barrier to the widespread clinical use of MCL1 inhibitors. This review explores the history and progress of MCL1 inhibition in MM through highlighting molecular methods of inhibition, early and current preclinical small molecule inhibitors, and past and present MCL1 inhibitor clinical trials for R/R MM.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.