Methods to prevent teratogenicity of imid like molecules and imid based degraders/protacs
AssigneeDana-Farber Cancer Institute, Inc.
InventorsEric S. Fischer, Katherine Donovan
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Abstract
Presented are methods of assessing the teratogenicity of agents by measuring the degradation of SALL4, and related compounds with reduced teratogenicity. Provided herein is a method for assessing the teratogenicity of an agent comprising: contacting an agent with SALL4; and measuring levels of SALL4, wherein the agent is teratogenic if SALL4 levels are substantially reduced in the presence of the agent relative to in the absence of the agent.
Claims26
A method for assessing the teratogenicity of an agent comprising:
- a) contacting an agent with Spalt-like transcription factor 4 (SALL4);
- and
- b1) measuring levels of SALL4,
- wherein the agent is teratogenic if SALL4 levels are substantially reduced in the presence of the agent relative to in the absence of the agent, or
- b2) measuring association of SALL4 with cereblon (CRBN),
- wherein the agent is teratogenic if SALL4 substantially associates with cereblon (CRBN) in the presence of the agent relative to in the absence of the agent, or
- b3) measuring ubiquitination of SALL4,
- wherein the agent is teratogenic if SALL4 is substantially ubiquitinated in the presence of the agent relative to in the absence of the agent, or
- b4) measuring degradation of SALL4,
- wherein the agent is teratogenic if SALL4 is substantially degraded in the presence of the agent relative to in the absence of the agent.
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A modified thalidomide, wherein the modified thalidomide does not cause substantial reduction of SALL4 levels, substantial association of SALL4 with CRBN, substantial ubiquitination of SALL4, or substantial degradation of SALL4 when contacted with SALL4 as compared to a thalidomide without the modification.
Dependencies are inferred from the claim text.