Chlorambucil

Summary

Chlorambucil (CHEMBL515) is an approved small-molecule alkylating agent (ATC L01AA02); indicated across 12 conditions including acute lymphoblastic leukemia and neoplasm; with CIViC clinical evidence for 1 variant-indication association (e.g. FANCC Loss-of-function in pancreatic cancer).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01AA02
• Indications: 12 conditions
• Clinical trials: 48
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 304.2 Da · C14H19Cl2NO2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL515
Name	Chlorambucil
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2708
ChEBI	CHEBI:28830
ATC	L01AA02
Molecular formula	C14H19Cl2NO2
Molecular weight	304.2
InChIKey	JCKYGMPEJWAADB-UHFFFAOYSA-N

SMILES: C1=CC(=CC=C1CCCC(=O)O)N(CCCl)CCCl

IUPAC name: 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoic acid

ChEBI definition: A monocarboxylic acid that is butanoic acid substituted at position 4 by a 4-[bis(2-chloroethyl)amino]phenyl group. A chemotherapy drug that can be used in combination with the antibody obinutuzumab for the treatment of chronic lymphocytic leukemia.

Pharmacological roles (ChEBI): alkylating agent, carcinogenic agent, antineoplastic agent, immunosuppressive agent, drug allergen.

Also known as: Ambochlorin, CB-1348, Chlorambucil, Chlorambucilum, Clorambucilo, Ecloril, Leukeran, Lympholysin, NCI-3088, NSC-3088, chlorambucil, SID11110896

Patent coverage: 41,227 distinct patent families (172,228 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Microtubule-associated protein tau, Survival motor neuron protein, Prelamin-A/C, Thrombopoietin, Geminin, Peripheral myelin protein 22, Solute carrier organic anion transporter family member 1B3, Thyrotropin receptor, Aldo-keto reductase family 1 member B1, Muscarinic acetylcholine receptor M1, Cytochrome P450 2D6, Nuclear factor NF-kappa-B p105 subunit, Aldehyde dehydrogenase 1A1, Hypoxia-inducible factor 1-alpha, Gamma-aminobutyric acid receptor subunit alpha-1/alpha-2/beta-2/gamma-2.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 32 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TSHR	6.2	Potency	631	nM	CHEMBL_ACT_3911493
TSHR	6.2	Potency	631	nM	CHEMBL_ACT_4710803
ALDH1A1	5.72	Potency	1887	nM	CHEMBL_ACT_4157269
HIF1A	5.3	Potency	5012	nM	CHEMBL_ACT_4125825
HIF1A	5.3	Potency	5012	nM	CHEMBL_ACT_4520034
LMNA	5.15	Potency	7080	nM	CHEMBL_ACT_3644166
NFKB1	5.05	Potency	8912	nM	CHEMBL_ACT_3675743
NFKB1	5.05	Potency	8912	nM	CHEMBL_ACT_4588925
P07943	5.03	IC50	9413	nM	CHEMBL_ACT_7681817
HIF1A	5	Potency	10000	nM	CHEMBL_ACT_4129698
HIF1A	5	Potency	10000	nM	CHEMBL_ACT_4518734
THPO	5	Potency	10000	nM	CHEMBL_ACT_4805540
THPO	5	Potency	10000	nM	CHEMBL_ACT_5070291

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

8 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
acute lymphoblastic leukemia	4	MONDO:0004967	EFO:0000220
neoplasm	4	MONDO:0005070	EFO:0000616
Hodgkins lymphoma	4	MONDO:0004952	EFO:0000183
B-cell chronic lymphocytic leukemia	3	MONDO:0004948	EFO:0000095
MALT lymphoma	3	MONDO:0007650	EFO:0000191
leukemia	3	MONDO:0005059	EFO:0000565
lymphoma	3	MONDO:0005062	EFO:0000574
gastric neoplasm	3	MONDO:0021085	MONDO:0001056

4 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
focal segmental glomerulosclerosis	3	MONDO:0100313	EFO:0004236
membranous glomerulonephritis	3	MONDO:0005376	EFO:0004254
mantle cell lymphoma	2	MONDO:0018876	EFO:1001469
pancreatic ductal adenocarcinoma	2	MONDO:0005184	MONDO:0005184

Clinical trials

Total trials: 48.

Phase distribution

Phase	Trials
PHASE3	29
PHASE2	9
PHASE1	3
Not specified	3
PHASE4	2
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01056510	PHASE4	COMPLETED	A Study of MabThera Added to Bendamustine or Chlorambucil in Patients With Chronic Lymphocytic Leukemia (MaBLe)
NCT01283386	PHASE4	TERMINATED	A Study to Compare Mabthera (Rituximab), Fludarabine and Cyclophosphamide to Mabthera and Chlorambucil in Participants With Chronic Lymphocytic Leukemia and Unfavorable Somatic Status
NCT02475681	PHASE3	ACTIVE_NOT_RECRUITING	Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL
NCT03462719	PHASE3	ACTIVE_NOT_RECRUITING	A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT04075292	PHASE3	ACTIVE_NOT_RECRUITING	Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia
NCT06319456	PHASE3	RECRUITING	A Global Study of Lisaftoclax (APG-2575) Combined With Acalabrutinib Versus Immunochemotherapy for Newly Diagnosed CLL/SLL.
NCT00003421	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Advanced Hodgkin’s Disease
NCT00003617	PHASE3	UNKNOWN	Chlorambucil Compared With No Further Therapy Following Anti-Helicobacter Therapy in Treating Patients With Low-Grade Lymphoma of the Stomach
NCT00003639	PHASE3	UNKNOWN	Combination Chemotherapy With or Without Interferon Alfa in Treating Patients With Low-Grade Non-Hodgkin’s Lymphoma
NCT00004218	PHASE3	COMPLETED	Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia
NCT00006250	PHASE3	UNKNOWN	Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Non-Hodgkin’s Lymphoma
NCT00017108	PHASE3	UNKNOWN	Chlorambucil in Treating Patients With Advanced Chronic Lymphocytic Leukemia
NCT00028691	PHASE3	UNKNOWN	Chlorambucil Compared With Radiation Therapy in Treating Patients With Previously Untreated Stage III or Stage IV Follicular Lymphoma
NCT00210353	PHASE3	COMPLETED	Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma
NCT00262795	PHASE3	COMPLETED	Fludarabine or Chlorambucil as First-Line Therapy in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia
NCT00404833	PHASE3	COMPLETED	Mycophenolate Mofetil in Membranous Nephropathy and Focal Segmental
NCT00566332	PHASE3	COMPLETED	Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia
NCT00608374	PHASE3	COMPLETED	Chlorambucil or Fludarabine as First-Line Therapy in Treating Patients With Previously Untreated Waldenström Macroglobulinemia, Splenic Lymphoma, or Lymphoplasmacytic Lymphoma
NCT00910910	PHASE3	COMPLETED	Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial)
NCT01010061	PHASE3	COMPLETED	CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 1a)
NCT01657955	PHASE3	UNKNOWN	Bendamustine Hydrochloride Injection for Previously Untreated Chronic Lymphocytic Leukemia
NCT01678430	PHASE3	UNKNOWN	A Trial Looking at Ofatumumab for People With Chronic Lymphocytic Leukaemia Who Cannot Have More Intensive Treatment
NCT01722487	PHASE3	COMPLETED	Open-label Phase 3 BTK Inhibitor Ibrutinib vs Chlorambucil Patients 65 Years or Older With Treatment-naive CLL or SLL
NCT01905943	PHASE3	COMPLETED	A Safety and Efficacy Study of Obinutuzumab Alone or in Combination With Chemotherapy in Participants With Chronic Lymphocytic Leukemia
NCT01980875	PHASE3	TERMINATED	Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
NCT01998880	PHASE3	COMPLETED	CLL11: A Study of Rituximab With Chlorambucil or Chlorambucil Alone in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 1b)
NCT02053610	PHASE3	COMPLETED	CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 2)
NCT02242942	PHASE3	COMPLETED	Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia
NCT02264574	PHASE3	COMPLETED	A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment naïve Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
NCT02612311	PHASE3	TERMINATED	Ublituximab + TGR-1202 Compared to Obinutuzumab + Chlorambucil in Participants With Untreated and Previously Treated Chronic Lymphocytic Leukemia
NCT04578613	PHASE3	UNKNOWN	ICP-022 Versus Chlorambucil Combined With Rituximab in the Treatment of Untreated CLL/SLL
NCT01808599	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Study of Chlorambucil and Subcutaneous Rituximab in Patients With Extranodal MALT Lymphoma
NCT00025064	PHASE2	UNKNOWN	Combination Chemotherapy With or Without Radiation Therapy and Peripheral Stem Cell Transplant in Treating Children With Hodgkin’s Lymphoma
NCT00151736	PHASE2	TERMINATED	Safety and Efficacy of SDX-101 (R-Etodolac) in Combination With Chlorambucil, and That of Chlorambucil Alone, in Patients With Chronic Lymphocytic Leukemia (CLL)
NCT00285389	PHASE2	COMPLETED	Treatment of Mantle Cell Lymphoma at Diagnosis for Patients Under 65 Years
NCT00532129	PHASE2	COMPLETED	A Study of MabThera (Rituximab) Plus Chlorambucil in Participants With Chronic Lymphocytic Leukemia.
NCT00558961	PHASE1/PHASE2	TERMINATED	Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients
NCT00738374	PHASE2	COMPLETED	A Study of MabThera (Rituximab) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia.
NCT01109264	PHASE2	COMPLETED	Bendamustine Hydrochloride Injection for Initial Treatment of Chronic Lymphocytic Leukemia
NCT01403246	PHASE1/PHASE2	TERMINATED	Chlorambucil + Lenalidomide and Lenalidomide Maintenance in Untreated Elderly With Chronic Lymphocytic Leukemia (CLL)
NCT01868893	PHASE2	COMPLETED	An Expanded Access, Open-Label Study of Obinutuzumab (GA101) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia
NCT04692740	PHASE2	UNKNOWN	Chlorambucil in Metastatic PDAC Patients Bearing a Germ Line DNA Defects Repair Mutations (SALE Trial)
NCT01088048	PHASE1	COMPLETED	Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Participants With Relapsed or Refractory Indolent B-cell Non-Hodgkin’s Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
NCT02100852	PHASE1	COMPLETED	TGR-1202, a PI3K Delta Inhibitor, in Combination With Obinutuzumab and Chlorambucil in Patients With Chronic Lymphocytic Leukemia (CLL)
NCT02336048	PHASE1	TERMINATED	A Study Evaluating the Safety of Tocilizumab in Addition to Standard of Care Premedication Given Before Obinutuzumab + Chlorambucil in Participants With Untreated B-Cell Chronic Lymphocytic Leukemia (B-CLL) and Comorbidities
NCT00416377	Not specified	UNKNOWN	Radiation Therapy or Combination Chemotherapy in Treating Young Patients With Hodgkin’s Lymphoma
NCT00417014	Not specified	UNKNOWN	Combination Chemotherapy and/or Radiation Therapy in Treating Young Patients With Hodgkin’s Lymphoma
NCT02915224	Not specified	COMPLETED	A Study of Obinutuzumab Evaluating Efficacy, Safety and Cost of Disease Management in Participants With Chronic Lymphocytic Leukemia and Comorbidities

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
FANCC Loss-of-function	Pancreatic Cancer	Sensitivity/Response	Cisplatin + Melphalan + Chlorambucil + Mitomycin + Gemcitabine	CIViC D	EID1307

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).