Friday, January 2, 2026 1/2/2026

Novel Small-Molecule Probes Targeting Oncogenic Fusion MLL in Pediatric Leukemia

Award Number: R01CA266057
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/10/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Novel Small-Molecule Probes Targeting Oncogenic Fusion MLL in Pediatric Leukemia - Acute leukemia, including acute myeloid (AML) and lymphoid leukemia (ALL), is the most common (1 out of 3) cancer in children and adolescents. Particularly, leukemia caused by chromosome translocations involving mixed lineage leukemia (MLL) gene accounts for ~75% of leukemia in infants and ~10% in children/adults with a poor prognosis. Compared to other pediatric ALL with a 5-year survival of ~90%, that for MLL-rearranged ALL is only ~40%, and for very young infants, the survival is even <20%. MLL-rearranged AML patients have similarly poor clinical outcomes to other AMLs. Current treatments are conventional chemo-drugs, which kill all rapidly proliferating cells including normal stem cells in bone marrow and other organs. This causes severe toxicities, side effects, and even secondary cancer due to mutagenesis. There is therefore a pressing need to find less toxic drugs targeting MLL-oncogene that drives the malignancy. MLL-oncogene consists of MLL fused with another gene. AF9 (~30%) and AF4 (35%) are the most frequent fusion partners of MLL. These proteins, together with DOT1L (a known drug target for the leukemia), associate with each other and constitute the so- called super elongation complex (SEC), which causes malignant gene expression in leukemia. Previous studies show the protein-protein interactions between AF9 and AF4 or DOT1L is critical to MLL-leukemia, but is dispensable in normal cells. This project aims to find and develop the first small-molecule inhibitors that disrupt the AF9-AF4/DOT1L interaction, which could be novel chemical probes for biological studies of AF9/SEC, or potential therapeutics for MLL-rearranged leukemia with a low toxicity. The Specific Aim 1 is to use rational design and medicinal chemistry to find potent, drug-like inhibitors of AF9. Aim 2 is to perform biochemical, X-ray and NMR structural studies to characterize inhibitor-AF9 interactions. Aim 3 is to perform cell-based assays to test biological activities of selected potent inhibitors, and Aim 4 is to perform pharmacokinetics, toxicity, and antitumor activity testing to identify useful chemical probes or potential drug candidates.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	4	10/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $437,571 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	001	4	6/4/2025	NON-COMPETING CONTINUATION	$43,757
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	4	11/12/2024	NON-COMPETING CONTINUATION	$393,814
														Subtotal = $437,571

Issue Date FY: 2024 ( Subtotal = $415,694 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	001	3	4/22/2024	NON-COMPETING CONTINUATION	$21,880
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	3	11/6/2023	NON-COMPETING CONTINUATION	$393,814
														Subtotal = $415,694

Issue Date FY: 2023 ( Subtotal = $428,820 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	001	2	3/14/2023	NON-COMPETING CONTINUATION	$35,006
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	2	11/18/2022	NON-COMPETING CONTINUATION	$393,814
														Subtotal = $428,820

Issue Date FY: 2022 ( Subtotal = $437,571 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	1	12/10/2021	NEW	$437,571
														Subtotal = $437,571

Grand Total All Awards = $1,719,656

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Novel Small-Molecule Probes Targeting Oncogenic Fusion MLL in Pediatric Leukemia

Award Number: R01CA266057

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/10/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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