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Chemical Structure| 2649400-34-8 Chemical Structure| 2649400-34-8

Structure of NX-5948
CAS No.: 2649400-34-8

Chemical Structure| 2649400-34-8

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NX-5948 is an orally active BTK degrader with antitumor activity. It can penetrate the blood-brain barrier and is effective against multiple BTK mutations, including resistant mutations.

Synonyms: BTK-IN-24

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Product Details of NX-5948

CAS No. :2649400-34-8
Formula : C42H54N12O5
M.W : 806.96
SMILES Code : O=C(C1=NC=C(N2C[C@H](N3CCN(C)C3=O)CCC2)N=C1NC4=CC=C(C5CCN(CC6CCN(C7=CC=C(C(N[C@@H](CC8)C(NC8=O)=O)=O)N=C7)CC6)CC5)C=C4)N
Synonyms :
BTK-IN-24
MDL No. :N/A

Safety of NX-5948

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Related Pathways of NX-5948

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
lymphoma cell lines < 1 nM (DC50) To assess the degradation of BTK in lymphoma cell lines. Results showed that NX-5948 catalyzes the degradation of 50% of cellular BTK (DC 50) at < 1 nM concentrations. Daniel W Robbins etal.
PBMCs < 1 nM (DC50) To assess the degradation of BTK in peripheral blood mononuclear cells (PBMCs). Results showed that NX-5948 catalyzes the degradation of 50% of cellular BTK (DC 50) at < 1 nM concentrations. Daniel W Robbins etal.
TMD8 cells < 10 nM (EC50) 72 hours To assess the impact of NX-5948 on cell viability in TMD8 cells. Results showed that NX-5948 impairs viability with an EC50 of < 10 nM.", Daniel W Robbins etal.
Ramos human Burkitt’s lymphoma B cells 10 nM 1, 2, 4, 6, 18, 24 hours To assess BTK degradation in Ramos human Burkitt’s lymphoma B cells. Results showed that BTK degradation is observed within 1 hour and is complete within 2 hours. Jeff Mihalic etal.
Primary human B cells 0.0001, 0.001, 0.01, 0.1, 1, 10, 100, 1000 nM To assess BTK degradation in primary human B cells. Results showed that NX-5948 achieved a DC50 of 0.034 nM. Jeff Mihalic etal.
TMD8 ABC DLBCL cells 50 nM 6 hours To assess the selectivity of NX-5948 for BTK in TMD8 ABC DLBCL cells. Results showed that NX-5948 is selective for BTK. Jeff Mihalic etal.
PBMCs Sub-nanomolar concentrations To assess the degradation of BTK and inhibition of BCR signaling in human PBMCs. Results showed that NX-5948 degrades BTK at sub-nanomolar concentrations and inhibits BCR signaling. D.Robbins etal.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice TMD8 xenograft model Oral Daily To assess the efficacy of NX-5948 in a TMD8 xenograft model. Results showed that daily oral administration of NX-5948 resulted in superior tumor growth inhibition (TGI) as compared to ibrutinib. Daniel W Robbins etal.
BALB/c mice TMD8 tumor model Oral 3, 10, 30 mg/kg Daily, 26 days To assess the efficacy of NX-5948 in a TMD8 tumor model. Results showed that NX-5948 significantly inhibited tumor growth at doses of 3, 10, and 30 mg/kg. Jeff Mihalic etal.
CD-1 mice and cynomolgus monkeys Collagen-induced arthritis (CIA) model Oral 10mg/kg Single dose To assess the degradation of BTK and anti-inflammatory activity in a CIA model. Results showed that NX-5948 resolved symptoms of arthritis, reduced arthritis clinical score, anti-type II collagen titer, and serum levels of IL-6. D.Robbins etal.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT05131022 Chronic Lymphocytic Leukemia (... More >>CLL)|Small Lymphocytic Lymphoma (SLL)|Diffuse Large B Cell Lymphoma (DLBCL)|Follicular Lymphoma (FL)|Mantle Cell Lymphoma (MCL)|Marginal Zone Lymphoma (MZL)|Waldenstrom Macroglobulinemia (WM)|Primary Central Nervous System Lymphoma (PCNSL)|Secondary Central Nervous System Lymphoma Less << PHASE1 RECRUITING 2025-01-28 City of Hope, Duarte, Californ... More >>ia, 91010, United States|University of California, San Francisco, San Francisco, California, 94143, United States|Yale Cancer Center, New Haven, Connecticut, 06510, United States|University of Miami, Miami, Florida, 33136, United States|Winship Cancer Institute of Emory University, Atlanta, Georgia, 30322, United States|Northwestern University, Chicago, Illinois, 60611, United States|Cayuga Medical Center, Ithaca, New York, 14850, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Duke University Medical Center, Durham, North Carolina, 27705, United States|University of Cincinnati Medical Center, Cincinnati, Ohio, 45219, United States|Cleveland Clinic, Cleveland, Ohio, 44195, United States|University of Pennsylvania, Abramson Cancer Center, Philadelphia, Pennsylvania, 19104, United States|MD Anderson Cancer Center, Houston, Texas, 77030, United States|Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, United States|University Medical Center Groningen, Groningen, 9713 GZ, Netherlands|Radboud University Medical Center, Nijmegen, 6525 GA, Netherlands|Erasmus MC, Rotterdam, 3015 GD, Netherlands|University Medical Center Utrecht, Utrecht, 3584 CX, Netherlands|Pratia SA, Warsaw, Mazowieckie, 02-172, Poland|Pratia MCM, Kraków, Ma?opolskie, 30-272, Poland|AidPort sp. Zo.o, Skorzewo, Wielkopolskie, 60-185, Poland|Pratia Onkologia Katowice, Katowice, ?l?skie, 40-519, Poland|Hospital Clínic de Barcelona, Barcelona, 08036, Spain|Hospital Ramón y Cajal, Madrid, 28034, Spain|Hospital Fundación Jimenez Díaz - START Madrid, Madrid, 28040, Spain|The Beatson WOS Cancer Center, Glasgow, Scotland, G12 0YN, United Kingdom|St. James Hospital, Leeds, LS9 7TF, United Kingdom|Clatterbridge Cancer Center NHS Foundation Trust, Liverpool, L7 8YA, United Kingdom|St. Bartholomew's Hospital, Barts NHS Trust, London, EC1A 7BE, United Kingdom|Sarah Cannon Research Institute UK, London, W1G 6AD, United Kingdom|The Christie NHS Foundation Trust, Manchester, M20 4BX, United Kingdom|Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, United Kingdom|University Hospitals Plymouth NHS Trust, Plymouth, PL6 8DH, United Kingdom|University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, United Kingdom|Royal Marsden NHS Foundation Trust, Sutton, SM2 5PT, United Kingdom Less <<
NCT06691828 Healthy Volunteer PHASE1 RECRUITING 2025-03-01 Celerion, Lincoln, Nebraska, 6... More >>8502, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.24mL

0.25mL

0.12mL

6.20mL

1.24mL

0.62mL

12.39mL

2.48mL

1.24mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
 

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