6-O-BENZYLGUANINE

Summary

6-O-Benzylguanine (CHEMBL407874) is a phase-3 clinical-stage small molecule; indicated across 12 conditions including neoplasm and cutaneous melanoma; with CIViC clinical evidence for 1 variant-indication association (e.g. MGMT Promoter Methylation in glioblastoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Indications: 12 conditions
• Clinical trials: 31
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 241.25 Da · C12H11N5O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL407874
Name	6-O-BENZYLGUANINE
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	4578
Molecular formula	C12H11N5O
Molecular weight	241.25
InChIKey	KRWMERLEINMZFT-UHFFFAOYSA-N

SMILES: C1=CC=C(C=C1)COC2=NC(=NC3=C2NC=N3)N

IUPAC name: 6-phenylmethoxy-7H-purin-2-amine

Also known as: NSC-637037, O(6)-benzylguanine, SID11110835, SID50105918, SID85230936, SID90341638, SID46500408, SID49674655, SID50105919, SID498466

Patent coverage: 2,144 distinct patent families (6,988 SureChEMBL compound mentions), from 5 matched compound structure(s). One matched structure accounts for 6,654 (95%) of the total. 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: Prelamin-A/C, RecQ-like DNA helicase BLM, Peripheral myelin protein 22, Cyclin-dependent kinase 1/cyclin B1, Thyrotropin receptor, Cyclin-dependent kinase 2/cyclin A, Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, Methylated-DNA–protein-cysteine methyltransferase, Cytochrome P450 2D6, Nuclear factor NF-kappa-B p105 subunit, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 3A4, Cytochrome P450 2C19, Dual specificity tyrosine-phosphorylation-regulated kinase 1A.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 29 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BLM	7.8	Potency	15.8	nM	CHEMBL_ACT_4749875
BLM	7.8	Potency	15.8	nM	CHEMBL_ACT_4933738
MGMT	7.41	IC50	39	nM	CHEMBL_ACT_12100717
MGMT	7.4	IC50	40	nM	CHEMBL_ACT_172632
MGMT	7.24	IC50	58	nM	CHEMBL_ACT_632130
PIN1	7.04	IC50	91.4	nM	CHEMBL_ACT_29151025
MGMT	7	IC50	100	nM	CHEMBL_ACT_172633
MGMT	6.75	IC50	180	nM	CHEMBL_ACT_632128
CYP2D6	6.3	Potency	501.2	nM	CHEMBL_ACT_4961618
CYP2D6	6.3	AC50	501.2	nM	CHEMBL_ACT_5987378
MGMT	6.21	IC50	620	nM	CHEMBL_ACT_148972
CYP1A2	6	AC50	1000	nM	CHEMBL_ACT_6063768
MGMT	5.58	IC50	2600	nM	CHEMBL_ACT_959344
TSHR	5.3	Potency	5012	nM	CHEMBL_ACT_3924556
Q63470	5.3	AC50	5050	nM	CHEMBL_ACT_7007594
NFKB1	5.25	Potency	5623	nM	CHEMBL_ACT_3675707
NFKB1	5.25	Potency	5623	nM	CHEMBL_ACT_4588889
CYP2C19	5.2	Potency	6310	nM	CHEMBL_ACT_4020226
CYP2C19	5.2	AC50	6310	nM	CHEMBL_ACT_6064735
CYP3A4	5.1	Potency	7943	nM	CHEMBL_ACT_4973519
CYP3A4	5.1	Potency	7943	nM	CHEMBL_ACT_5042509
CYP3A4	5.1	AC50	7943	nM	CHEMBL_ACT_6061634

Target pathways

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

Indications & clinical

Indications

12 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
neoplasm	3	MONDO:0005070	EFO:0000616
cutaneous melanoma	2	MONDO:0005012	EFO:0000389
glioblastoma	2	MONDO:0018177	EFO:0000519
sarcoma	2	MONDO:0005089	EFO:0000691
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
gliosarcoma	2	MONDO:0016681	EFO:1001465
central nervous system neoplasm	2	MONDO:0006130	EFO:1000158
colorectal neoplasm	2	MONDO:0005335	MONDO:0005575
lymphoma	1	MONDO:0005062	EFO:0000574
primary cutaneous T-cell non-Hodgkin lymphoma	1	MONDO:0000607	EFO:0002913
Sezary syndrome	1	MONDO:0017844	EFO:1000785
mycosis fungoides	1	MONDO:0009691	EFO:1001051

Clinical trials

Total trials: 31.

Phase distribution

Phase	Trials
PHASE1	16
PHASE2	10
PHASE1/PHASE2	2
Not specified	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00017147	PHASE3	COMPLETED	S0001 RT and Carmustine With or Without O6BG in Patients With New Glioblastoma Multiforme or Gliosarcoma
NCT05052957	PHASE2	RECRUITING	hSTAR GBM (Hematopoetic Stem Cell (HPC) Rescue for GBM)
NCT00004072	PHASE2	COMPLETED	O6-benzylguanine And Carmustine in Treating Patients With Multiple Myeloma
NCT00005066	PHASE2	COMPLETED	O6-benzylguanine and Carmustine in Treating Patients With Recurrent, Metastatic, or Locally Advanced Soft Tissue Sarcoma
NCT00005081	PHASE2	COMPLETED	Carmustine Plus O6-benzylguanine in Treating Patients With Recurrent or Progressive Glioma
NCT00005961	PHASE2	COMPLETED	O6-benzylguanine and Carmustine in Treating Patients With Unresectable Locally Recurrent or Metastatic Melanoma
NCT00005981	PHASE2	COMPLETED	Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer
NCT00046878	PHASE2	WITHDRAWN	Carmustine and O(6)-Benzylguanine in Treating Patients With Newly Diagnosed Supratentorial Glioblastoma Multiforme
NCT00275002	PHASE2	COMPLETED	O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors
NCT00389090	PHASE2	TERMINATED	A Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma
NCT00436436	PHASE2	TERMINATED	O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy
NCT00669669	PHASE1/PHASE2	TERMINATED	O6-Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cell in Treating Patients With Malignant Gliomas
NCT00961220	PHASE1/PHASE2	COMPLETED	O6-Benzylguanine and Topical Carmustine in Treating Patients With Early-Stage IA-IIA Cutaneous T-Cell Lymphoma
NCT00002604	PHASE1	COMPLETED	O(6)-Benzylguanine and Carmustine in Treating Patients With Solid Tumors
NCT00002971	PHASE1	COMPLETED	O(6)-Benzylguanine in Treating Patients With Malignant Glioma
NCT00003348	PHASE1	COMPLETED	Carmustine Plus O(6)-Benzylguanine in Treating Patients With Recurrent or Progressive Gliomas of the Brain
NCT00003567	PHASE1	TERMINATED	Gene Therapy and Chemotherapy in Treating Patients With Advanced Solid Tumors or Non-Hodgkin’s Lymphoma
NCT00003613	PHASE1	TERMINATED	O6-benzylguanine and Carmustine in Treating Patients With Stage IA-IIA Cutaneous T-cell Lymphoma
NCT00003765	PHASE1	COMPLETED	O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors
NCT00003766	PHASE1	COMPLETED	O6-benzylguanine Followed by Surgery in Treating Patients With Solid Tumors That Can Be Removed During Surgery
NCT00004892	PHASE1	COMPLETED	O6-Benzylguanine and Carmustine Implants in Treating Patients With Recurrent Malignant Glioma
NCT00006474	PHASE1	COMPLETED	Temozolomide and O6-benzylguanine in Treating Patients With Newly Diagnosed, Recurrent, or Progressive Anaplastic Glioma
NCT00020150	PHASE1	COMPLETED	Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors
NCT00045721	PHASE1	TERMINATED	Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma
NCT00052780	PHASE1	COMPLETED	Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors
NCT00086970	PHASE1	TERMINATED	Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors
NCT00612989	PHASE1	COMPLETED	Ph I 5-day Temozolomide + O6-BG in Treatment of Pts w Recurrent / Progressive GBM
NCT01269424	PHASE1	COMPLETED	BG & TMZ Therapy of Glioblastoma Multiforme
NCT02343666	PHASE1	WITHDRAWN	HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection
NCT00253487	Not specified	COMPLETED	Combination Chemotherapy and Radiation Therapy in Treating Younger Patients Who Are Undergoing an Autologous Stem Cell Transplant for Newly Diagnosed Gliomas
NCT01769911	Not specified	WITHDRAWN	Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

Clinical evidence (CIViC)

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

Variant	Indication	Effect	Therapy	Level	CIViC
MGMT Promoter Methylation	Glioblastoma	Sensitivity/Response	O6-Benzylguanine	CIViC E	EID309

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

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