Diffuse intrinsic pontine glioma

Summary

Diffuse intrinsic pontine glioma (MONDO:0006033) is a cancer with 3 cohort genes (3 CIViC-evidence somatic drivers; 3 ClinVar predisposition records) and 108 clinical trials. Top therapeutic interventions include ribociclib, valproic acid, and atovaquone.

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (Netherlands) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 3
• Clinical trials: 108

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.056	Netherlands	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	diffuse intrinsic pontine glioma
Mondo ID	MONDO:0006033
EFO	EFO:1000026
MeSH	D000080443
Orphanet	497188
NCIT	C94764
UMLS	C2986658
MedGen	458884
GARD	0013075
Anatomy (UBERON)	UBERON:0000988
Is cancer (heuristic)	yes

Also known as: diffuse midline glioma · DIPG · infiltrative brainstem glioma

Data availability: 3 ClinVar variants · 46 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: neoplastic disease or syndrome › neoplasm › cancer › nervous system cancer › central nervous system cancer › brain cancer › infratentorial cancer › brainstem cancer › brain stem glioma › childhood brain stem glioma › diffuse intrinsic pontine glioma

Related subtypes (1): childhood brainstem astrocytoma

Subtypes (1): diffuse midline glioma, H3 K27-altered

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
51653	NM_000059.4(BRCA2):c.4478_4481del (p.Glu1493fs)	BRCA2	Pathogenic	reviewed by expert panel
30535	NM_032043.3(BRIP1):c.1045G>C (p.Ala349Pro)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
220148	NM_001042492.3(NF1):c.1888G>A (p.Val630Ile)	NF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 23 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
BRIP1			CIViC #15955
NF1	LoF	ACC,ALL,AML,ANGS,BLCA,BRCA,CCRCC,CHOL,CLLSLL,COADREAD,GB,GBM,GIST,HCC,HNSC,LGGNOS,LMS,LUAD,LUNG,LUSC,MEL,NBL,NSCLC,OVT,PAST,PGNG,PLMESO,RMS,SKCM,SOFT_TISSUE,STAD,THYM,UCS	CIViC #3867

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
BRIP1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRIP1	Orphanet:84	Fanconi anemia
NF1	Orphanet:139474	17q11.2 microduplication syndrome
NF1	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
NF1	Orphanet:293199	Pleomorphic rhabdomyosarcoma
NF1	Orphanet:363700	Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion
NF1	Orphanet:638	Neurofibromatosis-Noonan syndrome
NF1	Orphanet:86834	Juvenile myelomonocytic leukemia
NF1	Orphanet:97685	17q11 microdeletion syndrome
NF1	Orphanet:99756	Alveolar rhabdomyosarcoma
NF1	Orphanet:99757	Embryonal rhabdomyosarcoma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
BRIP1	HGNC:20473	ENSG00000136492	Q9BX63	Fanconi anemia group J protein	clinvar
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
BRIP1	Fanconi anemia group J protein	DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
BRIP1	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
ventricular zone	2
secondary oocyte	1
primordial germ cell in gonad	1
adrenal tissue	1
calcaneal tendon	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
BRIP1	181	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NF1	5,540
BRCA2	4,839
BRIP1	2,272

Intra-cohort edges

A	B	Sources
BRCA2	BRIP1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NF1	P21359	26
BRCA2	P51587	14
BRIP1	Q9BX63	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 binding to PALB2	2	304.5×	1e-04	BRCA2, BRIP1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	282.0×	1e-04	BRCA2, BRIP1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	282.0×	1e-04	BRCA2, BRIP1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	282.0×	1e-04	BRCA2, BRIP1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	262.5×	1e-04	BRCA2, BRIP1
Homologous DNA Pairing and Strand Exchange	2	253.8×	1e-04	BRCA2, BRIP1
Impaired BRCA2 binding to RAD51	2	205.8×	2e-04	BRCA2, BRIP1
Resolution of D-loop Structures through Holliday Junction Intermediates	2	200.3×	2e-04	BRCA2, BRIP1
Presynaptic phase of homologous DNA pairing and strand exchange	2	181.3×	2e-04	BRCA2, BRIP1
HDR through Homologous Recombination (HRR)	2	126.9×	3e-04	BRCA2, BRIP1
Impaired BRCA2 translocation to the nucleus	1	1268.9×	0.003	BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)	1	1268.9×	0.003	BRCA2
RAS signaling downstream of NF1 loss-of-function variants	1	543.8×	0.006	NF1
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	317.2×	0.009	BRCA2
HDR through MMEJ (alt-NHEJ)	1	292.8×	0.009	BRCA2
Diseases of DNA Double-Strand Break Repair	1	271.9×	0.009	BRCA2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	271.9×	0.009	BRCA2
Cytosolic iron-sulfur cluster assembly	1	253.8×	0.009	BRIP1
Resolution of D-Loop Structures	1	211.5×	0.010	BRCA2
Diseases of DNA repair	1	190.3×	0.010	BRCA2
Homology Directed Repair	1	102.9×	0.017	BRCA2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	102.9×	0.017	BRCA2
HDR through Single Strand Annealing (SSA)	1	97.6×	0.017	BRIP1
Meiosis	1	95.2×	0.017	BRCA2
DNA Double-Strand Break Repair	1	82.8×	0.019	BRCA2
Oncogenic MAPK signaling	1	82.8×	0.019	NF1
Regulation of RAS by GAPs	1	64.5×	0.022	NF1
Reproduction	1	63.4×	0.022	BRCA2
Disease	2	8.7×	0.023	BRCA2, NF1
MAPK1/MAPK3 signaling	1	43.8×	0.030	NF1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nucleotide-excision repair	2	255.3×	0.003	BRCA2, BRIP1
positive regulation of mast cell apoptotic process	1	5617.3×	0.004	NF1
regulation of glial cell differentiation	1	5617.3×	0.004	NF1
observational learning	1	5617.3×	0.004	NF1
gamma-aminobutyric acid secretion, neurotransmission	1	2808.7×	0.004	NF1
mitotic recombination-dependent replication fork processing	1	2808.7×	0.004	BRCA2
meiotic DNA double-strand break processing involved in reciprocal meiotic recombination	1	1872.4×	0.004	BRIP1
Schwann cell proliferation	1	1872.4×	0.004	NF1
forebrain astrocyte development	1	1872.4×	0.004	NF1
Schwann cell migration	1	1872.4×	0.004	NF1
glutamate secretion, neurotransmission	1	1872.4×	0.004	NF1
negative regulation of mast cell proliferation	1	1872.4×	0.004	NF1
negative regulation of Schwann cell migration	1	1872.4×	0.004	NF1
vascular associated smooth muscle cell migration	1	1872.4×	0.004	NF1
double-strand break repair	2	135.4×	0.004	BRCA2, BRIP1
brain development	2	53.0×	0.004	BRCA2, NF1
mast cell apoptotic process	1	1404.3×	0.005	NF1
negative regulation of Rac protein signal transduction	1	1404.3×	0.005	NF1
myeloid leukocyte migration	1	1404.3×	0.005	NF1
spermatogonial cell division	1	1123.5×	0.005	BRIP1
negative regulation of mammary gland epithelial cell proliferation	1	1123.5×	0.005	BRCA2
mast cell proliferation	1	1123.5×	0.005	NF1
amygdala development	1	936.2×	0.006	NF1
regulation of blood vessel endothelial cell migration	1	936.2×	0.006	NF1
vascular associated smooth muscle cell proliferation	1	936.2×	0.006	NF1
negative regulation of Schwann cell proliferation	1	802.5×	0.006	NF1
negative regulation of neurotransmitter secretion	1	802.5×	0.006	NF1
hair follicle maturation	1	702.2×	0.007	NF1
establishment of protein localization to telomere	1	702.2×	0.007	BRCA2
chiasma assembly	1	624.1×	0.007	BRIP1

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Nimotuzumab	Phase 3 (in late-stage trials)
Temozolomide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bevacizumab, Dasatinib Anhydrous, Erlotinib, Everolimus, PEGINTERFERON ALFA-2A, Panobinostat, Vinorelbine.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRCA2	0	0
BRIP1	0	0
NF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRIP1	3.6.4.12	DNA helicase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	BRIP1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	BRCA2, NF1

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	—
BRIP1	0	—
NF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 108.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	49
PHASE1/PHASE2	20
PHASE2	19
Not specified	11
EARLY_PHASE1	6
PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05476939	PHASE3	RECRUITING	Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0
NCT03243461	PHASE3	UNKNOWN	International Cooperative Phase III Trial of the HIT-HGG Study Group (HIT-HGG-2013)
NCT04532229	PHASE3	UNKNOWN	Nimotuzumab in Combined With Chemoradiotherapy to Treat the Newly Diagnosed Diffuse Intrinsic Pontine Glioma in Children
NCT03709680	PHASE2	ACTIVE_NOT_RECRUITING	Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
NCT04049669	PHASE2	ACTIVE_NOT_RECRUITING	Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
NCT04250064	PHASE2	RECRUITING	A Study of Low Dose Bevacizumab With Conventional Radiotherapy Alone in Diffuse Intrinsic Pontine Glioma
NCT04758533	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Clinical Trial to Assess the Safety and Efficacy of AloCELYVIR With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) in Combination With Radiotherapy or Medulloblastoma in Monotherapy
NCT04870944	PHASE1/PHASE2	RECRUITING	CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
NCT04911621	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Adjuvant Dendritic Cell Immunotherapy for Pediatric Patients With High-grade Glioma or Diffuse Intrinsic Pontine Glioma
NCT05009992	PHASE2	RECRUITING	Combination Therapy for the Treatment of Diffuse Midline Gliomas
NCT05096481	PHASE2	RECRUITING	PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly Diagnosed Pediatric HGG and DIPG and Recurrent Medulloblastoma
NCT05278208	PHASE1/PHASE2	RECRUITING	Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors
NCT05843253	PHASE2	RECRUITING	Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant
NCT05956821	PHASE1/PHASE2	RECRUITING	Treatment of Relapsed/Refractory Intracranial Glioma in Patients Under 22 Years of Age
NCT06161974	PHASE2	RECRUITING	Study of Olutasidenib and Temozolomide in HGG
NCT06465199	PHASE1/PHASE2	RECRUITING	Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas
NCT06521567	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Cobolimab Plus Dostarlimab in Pediatric and Young Adult Participants With Cancer
NCT06607692	PHASE1/PHASE2	RECRUITING	Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined With the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).
NCT06639607	PHASE1/PHASE2	NOT_YET_RECRUITING	PEP-CMV + Nivolumab for Newly Diagnosed Diffuse Midline Glioma/High-grade Glioma and Recurrent Diffuse Midline Glioma/High-grade Glioma, Medulloblastoma, and Ependymoma
NCT06838676	PHASE2	RECRUITING	ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas
NCT07206849	PHASE2	NOT_YET_RECRUITING	Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)
NCT07501156	PHASE1/PHASE2	RECRUITING	H3K27M-specific Immune Effector Cells Targeting DMG/DIPG
NCT07589257	PHASE2	RECRUITING	A Study of VRT106 in Combination With Radiotherapy in Adult Patients With Diffuse Midline Glioma / Diffuse Intrinsic Pontine Glioma
NCT00036569	PHASE2	COMPLETED	A Phase II Study of Pegylated Interferon Alfa 2b (PEG-Intron(Trademark)) in Children With Diffuse Pontine Gliomas
NCT00879437	PHASE2	COMPLETED	Valproic Acid, Radiation, and Bevacizumab in Children With High Grade Gliomas or Diffuse Intrinsic Pontine Glioma
NCT01182350	PHASE2	TERMINATED	Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG)
NCT01189266	PHASE1/PHASE2	COMPLETED	Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma
NCT01837862	PHASE1/PHASE2	COMPLETED	A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas
NCT01884740	PHASE1/PHASE2	TERMINATED	Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22
NCT01952769	PHASE1/PHASE2	UNKNOWN	Anti PD1 Antibody in Diffuse Intrinsic Pontine Glioma
NCT02233049	PHASE2	UNKNOWN	Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication
NCT02525692	PHASE2	TERMINATED	Oral ONC201 in Adult Recurrent Glioblastoma
NCT02607124	PHASE1/PHASE2	TERMINATED	A Phase I/II Study of Ribociclib,a CDK4/6 Inhibitor, Following Radiation Therapy
NCT02750891	PHASE1/PHASE2	COMPLETED	A Study of DSP-7888 in Pediatric Patients With Relapsed or Refractory High Grade Gliomas
NCT02758366	PHASE2	TERMINATED	Prolonged Exposure to Doxorubicin in Patients With Glioblastoma Multiforme and Diffuse Intrinsic Pontine Glioma
NCT02960230	PHASE1/PHASE2	COMPLETED	H3.3K27M Peptide Vaccine With Nivolumab for Children With Newly Diagnosed DIPG and Other Gliomas
NCT03330197	PHASE1/PHASE2	TERMINATED	A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG
NCT03566199	PHASE1/PHASE2	COMPLETED	MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma
NCT03620032	PHASE2	UNKNOWN	Study of Re-irradiation at Relapse Versus RT and Multiple Elective rt Courses
NCT03632317	PHASE2	WITHDRAWN	A Study of Panobinostat in Combination With Everolimus for Children and Young Adults With Gliomas

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RIBOCICLIB	4	2
VALPROIC ACID	4	2
ATOVAQUONE	4	1
CEMIPLIMAB	4	1
CRIZOTINIB	4	1
DOSTARLIMAB	4	1
EFLORNITHINE	4	1
LAROTRECTINIB	4	1
LOMUSTINE	4	1
LORLATINIB	4	1
LUTETIUM OXODOTREOTIDE LU-177	4	1
MEBENDAZOLE	4	1
MELPHALAN HYDROCHLORIDE	4	1
OLUTASIDENIB	4	1
PANOBINOSTAT	4	1
TEMOZOLOMIDE	4	1
TOVORAFENIB	4	1
VANDETANIB	4	1
VORINOSTAT	4	1
DORDAVIPRONE	3	4
BALSTILIMAB	3	1
BECOTATUG VEDOTIN	3	1
CILENGITIDE	3	1
CRENOLANIB	3	1
DISUFENTON SODIUM	3	1
MARIZOMIB	3	1
NIMOTUZUMAB	3	1
OMBIPEPIMUT-S	3	1
SAVOLITINIB	3	1
INDOXIMOD	2	2