Methods of use for trisubstituted benzotriazole derivatives
Inventors
Ulanet, Danielle • Choe, Sung Eun
Assignees
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Publication Number
US-12290508-B2
Publication Date
2025-05-06
Expiration Date
Abstract
The present invention provides methods for treating cancer in a subject with a trisubstituted benzotriazole derivative with the formula (I)or a pharmaceutically acceptable salt thereof, wherein the variables R1, R2 and R3 are as defined herein.
Core Innovation
The invention relates to methods for treating cancers using trisubstituted benzotriazole derivatives represented by formula (I), or pharmaceutically acceptable salts or compositions thereof. Therapeutically effective amounts are administered to a subject to achieve anticancer treatment.
The problem addressed is the need for cancer treatment options, including treatment of chemotherapy-resistant and cytarabine-resistant cancers. The document specifically targets double-hit and triple-hit diffuse large B cell lymphoma, including patient-derived DLBCL models.
The invention is supported by experimental observations reported as growth inhibition and in vivo efficacy. In vitro profiling includes sensitivity subsets and comparative profiles versus cytarabine and doxorubicin, and in vivo results in patient-derived DLBCL xenografts include dose/schedule-dependent inhibition with biomarker changes including DHO and uridine pools, including in a triple-hit DLBCL PDX model.
Claims Coverage
The document provides two independent claim sets covering administering a therapeutically effective amount of a compound or pharmaceutically acceptable salt defined by a specific structural formula to treat double hit diffuse large B cell lymphoma and/or triple hit diffuse large B cell lymphoma. Across the independent claims, the main inventive content is the defined trisubstituted benzotriazole derivative structure (formula (I) substituent framework) and the corresponding therapeutic use in the specified DLBCL subtypes.
Treating double hit or triple hit DLBCL with formula (I) benzotriazole derivatives
A method of treating double hit diffuse large B cell lymphoma or triple hit diffuse large B cell lymphoma in a subject by administering a therapeutically effective amount of a compound represented by a structural formula (I) or a pharmaceutically acceptable salt thereof, where the dotted lines represent an optional bond in a stable combination and where substituent variables R1, R2, R3, R4, R5, Ra, Rb, and n are selected according to the defined options.
Treating double hit DLBCL with the therapeutically effective compound
A method of treating double hit diffuse large B cell lymphoma by administering to the subject a therapeutically effective amount of the compound of a specified structural formula or a pharmaceutically acceptable salt thereof.
Overall claim coverage centers on therapeutic methods for double hit and triple hit diffuse large B cell lymphoma using a compound represented by a defined trisubstituted benzotriazole structural formula (I), including pharmaceutically acceptable salts.
Stated Advantages
Treats double hit diffuse large B cell lymphoma and triple hit diffuse large B cell lymphoma.
Reported activity includes dose/schedule-dependent inhibition and high levels of tumor growth inhibition in a triple-hit DLBCL PDX model, with biomarker changes including DHO levels and uridine pools.
Documented Applications
Treatment application explicitly described in the claims and summary for double hit diffuse large B cell lymphoma and triple hit diffuse large B cell lymphoma in a subject.
Patient-derived DLBCL xenograft efficacy application described for double-hit and triple-hit DLBCL models, including an OCILY-19 model and a triple-hit DLBCL PDX model with biomarker changes including DHO levels and uridine pools.
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