FNTA

Summary

FNTA (farnesyltransferase, CAAX box, subunit alpha, HGNC:3782) is a protein-coding gene on chromosome 8p11.21, encoding Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (P49354). Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. It is a common-essential gene (DepMap: required in 90.7% of cancer cell lines).

Prenyltransferases can attach either a farnesyl group or a geranylgeranyl group in thioether linkage to the cysteine residue of proteins with a C-terminal CAAX box. CAAX geranylgeranyltransferase and CAAX farnesyltransferase are heterodimers that share the same alpha subunit but have different beta subunits. This gene encodes the alpha subunit of these transferases. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 11 and 13.

Source: NCBI Gene 2339 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 75 total — 1 pathogenic
• GTEx eGene: eQTL in 31 tissues, sQTL in 3 (q < 0.05)
• Drug target: yes — 2 via a complex or family; 6 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 1 — Lonafarnib (Protein farnesyltransferase)
• Cancer dependency (DepMap): dependent in 90.7% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.43 (unconstrained)
• MANE Select transcript: NM_002027
• Notable: 75 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3782
Approved symbol	FNTA
Name	farnesyltransferase, CAAX box, subunit alpha
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Aliases	FPTA, PGGT1A, PTAR2
Ensembl gene	ENSG00000168522
Ensembl biotype	protein_coding
OMIM	134635
Entrez	2339

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 19 protein_coding, 14 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000302279

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 4, TSL 3: 5, TSL 5: 3

ENST00000302279, ENST00000524546, ENST00000525099, ENST00000525699, ENST00000526755, ENST00000527153, ENST00000528400, ENST00000529687, ENST00000531266, ENST00000533336, ENST00000533368, ENST00000533383, ENST00000533559, ENST00000533998, ENST00000903292, ENST00000903293, ENST00000903294, ENST00000903295, ENST00000903296, ENST00000978808, ENST00000978810, ENST00000978811, ENST00000978812, ENST00000978813, ENST00000978814, ENST00000978815, ENST00000978816, ENST00000978817, ENST00000978818, ENST00001046954, ENST00001046955, ENST00001046956, ENST00001046957, ENST00001046958, ENST00001099793, ENST00001099794, ENST00001107143, ENST00001107144, ENST00001132870

RefSeq mRNA: 1 — MANE Select: NM_002027 NM_002027

CCDS: CCDS6140

Canonical transcript exons

ENST00000302279 — 9 exons

Exon	Start	End
ENSE00002156549	43056323	43056546
ENSE00003467132	43059092	43059177
ENSE00003487643	43085160	43085785
ENSE00003496632	43064101	43064215
ENSE00003499158	43083118	43083180
ENSE00003500721	43069555	43069659
ENSE00003514597	43077216	43077364
ENSE00003531863	43084710	43084881
ENSE00003790940	43072181	43072307

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.2743 / max 315.5645, expressed in 1825 samples.

Highest expression (Bgee): esophagus squamous epithelium, gingival epithelium, olfactory bulb, subthalamic nucleus, inferior vagus X ganglion.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FNTA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	6.5e-34	+0.71	8:43056843:T:A
Artery Aorta	eqtl	2.2e-20	-0.47	8:43061695:T:A
Thyroid	eqtl	3.3e-17	-0.38	8:42842898:A:G
Artery Tibial	eqtl	7.2e-15	-0.30	8:42912365:C:CTT
Adipose Subcutaneous	eqtl	9.2e-13	-0.32	8:43051014:T:G
Heart Left Ventricle	eqtl	2.4e-12	-0.29	8:43030212:C:A
Heart Atrial Appendage	eqtl	1.4e-10	-0.41	8:43030212:C:A
Adipose Visceral Omentum	eqtl	9.5e-10	-0.33	8:43250986:A:G
Esophagus Muscularis	eqtl	4.0e-09	-0.23	8:42967151:C:G
Nerve Tibial	eqtl	5.1e-09	+0.16	8:43150103:C:T
Muscle Skeletal	eqtl	1.9e-08	-0.21	8:43262278:C:T
Esophagus Gastroesophageal Junction	eqtl	3.3e-07	-0.27	8:42991527:T:C
Lung	eqtl	5.9e-07	-0.22	8:43030212:C:A
Cells Cultured fibroblasts	eqtl	2.0e-06	-0.30	8:42968337:G:T
Esophagus Mucosa	eqtl	4.7e-06	+0.16	8:43157491:C:CT
Artery Coronary	eqtl	9.8e-06	-0.44	8:43261590:A:G
Colon Sigmoid	eqtl	1.1e-05	-0.25	8:43260603:A:T
Cells EBV-transformed lymphocytes	eqtl	1.2e-05	+0.24	8:43056843:T:A
Breast Mammary Tissue	eqtl	3.0e-05	-0.23	8:43431538:C:T
Small Intestine Terminal Ileum	eqtl	5.4e-05	-0.31	8:42821960:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
88713	41.7047	1825
88714	3.5696	1547

Top tissues by expression

showing 100 of 298 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	99.20	gold quality
gingival epithelium	UBERON:0001949	99.19	gold quality
olfactory bulb	UBERON:0002264	99.12	gold quality
subthalamic nucleus	UBERON:0001906	99.09	gold quality
inferior vagus X ganglion	UBERON:0005363	99.07	gold quality
gingiva	UBERON:0001828	99.03	gold quality
squamous epithelium	UBERON:0006914	98.94	gold quality
pancreatic ductal cell	CL:0002079	98.84	gold quality
amniotic fluid	UBERON:0000173	98.83	gold quality
parotid gland	UBERON:0001831	98.82	gold quality
skin of hip	UBERON:0001554	98.81	gold quality
germinal epithelium of ovary	UBERON:0001304	98.80	gold quality
trigeminal ganglion	UBERON:0001675	98.76	gold quality
medulla oblongata	UBERON:0001896	98.70	gold quality
pons	UBERON:0000988	98.67	gold quality
corpus callosum	UBERON:0002336	98.63	gold quality
cranial nerve II	UBERON:0000941	98.56	gold quality
oral cavity	UBERON:0000167	98.52	gold quality
upper leg skin	UBERON:0004262	98.51	gold quality
parietal pleura	UBERON:0002400	98.50	gold quality
lateral globus pallidus	UBERON:0002476	98.50	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.48	gold quality
superior vestibular nucleus	UBERON:0007227	98.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.45	gold quality
dorsal root ganglion	UBERON:0000044	98.44	gold quality
epithelium of esophagus	UBERON:0001976	98.44	gold quality
epithelial cell of pancreas	CL:0000083	98.42	gold quality
mammalian vulva	UBERON:0000997	98.42	gold quality
pleura	UBERON:0000977	98.38	gold quality
inferior olivary complex	UBERON:0002127	98.37	gold quality
spinal cord	UBERON:0002240	98.37	gold quality
ventral tegmental area	UBERON:0002691	98.36	gold quality
cartilage tissue	UBERON:0002418	98.34	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.31	gold quality
renal glomerulus	UBERON:0000074	98.29	gold quality
tibia	UBERON:0000979	98.29	gold quality
visceral pleura	UBERON:0002401	98.24	gold quality
epithelium of nasopharynx	UBERON:0001951	98.18	gold quality
substantia nigra pars compacta	UBERON:0001965	98.18	gold quality
metanephric glomerulus	UBERON:0004736	98.17	gold quality
tendon of biceps brachii	UBERON:0008188	98.15	gold quality
middle frontal gyrus	UBERON:0002702	98.14	gold quality
upper arm skin	UBERON:0004263	98.11	gold quality
pericardium	UBERON:0002407	98.10	gold quality
tongue squamous epithelium	UBERON:0006919	98.10	gold quality
mammary duct	UBERON:0001765	98.05	gold quality
jejunal mucosa	UBERON:0000399	98.00	gold quality
biceps brachii	UBERON:0001507	98.00	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.99	gold quality
endothelial cell	CL:0000115	97.93	gold quality
epithelium of mammary gland	UBERON:0003244	97.93	gold quality
corpus epididymis	UBERON:0004359	97.91	gold quality
seminal vesicle	UBERON:0000998	97.88	gold quality
caput epididymis	UBERON:0004358	97.88	gold quality
globus pallidus	UBERON:0001875	97.87	gold quality
palpebral conjunctiva	UBERON:0001812	97.86	gold quality
deltoid	UBERON:0001476	97.85	gold quality
trabecular bone tissue	UBERON:0002483	97.81	gold quality
mammary gland	UBERON:0001911	97.80	gold quality
thoracic mammary gland	UBERON:0005200	97.79	gold quality
heart right ventricle	UBERON:0002080	97.77	gold quality
jejunum	UBERON:0002115	97.77	gold quality
penis	UBERON:0000989	97.76	gold quality
tongue	UBERON:0001723	97.76	gold quality
superior surface of tongue	UBERON:0007371	97.76	gold quality
eye	UBERON:0000970	97.72	gold quality
tibialis anterior	UBERON:0001385	97.71	gold quality
hair follicle	UBERON:0002073	97.71	gold quality
cervix squamous epithelium	UBERON:0006922	97.69	gold quality
medial globus pallidus	UBERON:0002477	97.67	gold quality
bronchial epithelial cell	CL:0002328	97.65	gold quality
pharyngeal mucosa	UBERON:0000355	97.59	gold quality
midbrain	UBERON:0001891	97.59	gold quality
body of tongue	UBERON:0011876	97.59	gold quality
endometrium	UBERON:0001295	97.55	gold quality
vastus lateralis	UBERON:0001379	97.55	gold quality
placenta	UBERON:0001987	97.52	gold quality
superficial temporal artery	UBERON:0001614	97.50	gold quality
substantia nigra	UBERON:0002038	97.49	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.47	gold quality
urethra	UBERON:0000057	97.46	gold quality
quadriceps femoris	UBERON:0001377	97.46	gold quality
gluteal muscle	UBERON:0002000	97.45	gold quality
cauda epididymis	UBERON:0004360	97.38	gold quality
epithelium of bronchus	UBERON:0002031	97.29	gold quality
synovial joint	UBERON:0002217	97.28	gold quality
pigmented layer of retina	UBERON:0001782	97.27	gold quality
choroid plexus epithelium	UBERON:0003911	97.26	gold quality
bronchus	UBERON:0002185	97.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.23	gold quality
tendon	UBERON:0000043	97.20	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.11	gold quality
adult organism	UBERON:0007023	97.10	gold quality
oviduct epithelium	UBERON:0004804	97.08	gold quality
metanephros	UBERON:0000081	97.03	gold quality
myocardium	UBERON:0002349	97.03	gold quality
layer of synovial tissue	UBERON:0007616	97.03	gold quality
tibial nerve	UBERON:0001323	97.01	gold quality
pylorus	UBERON:0001166	96.98	gold quality
vena cava	UBERON:0004087	96.97	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	138.8
Spinal cord	tissue	111.4
Medulla oblongata	tissue	83.0
Midbrain	tissue	77.9
Substantia nigra	tissue	77.4
Superior colliculi	tissue	65.4
Pons	tissue	64.2
Thalamus	tissue	63.1
Tongue	tissue	60.3
Periaqueductal gray	tissue	59.3
Skeletal muscle	tissue	56.1	medium
Putamen	tissue	55.9
Hypothalamus	tissue	48.7
Vagina	tissue	47.4	high
Ventral forebrain	tissue	47.3
Placenta	tissue	47.0	high
Adipose tissue	tissue	46.5	medium
Hippocampal formation	tissue	44.6
Liver	tissue	44.1	medium
Lymph node	tissue	42.6	medium
Septum	tissue	41.6
Breast	tissue	41.5	medium
Tonsil	tissue	41.4	high
Epididymis	tissue	40.8	medium
Pituitary gland	tissue	39.9
Heart muscle	tissue	39.5	high
Caudate putamen	tissue	39.4
Skin 1	tissue	38.9	high
Thymus	tissue	37.2
Ovary	tissue	36.4	medium
Cervix	tissue	35.9	high
Esophagus	tissue	35.9	medium
Spleen	tissue	34.6	medium
Pancreas	tissue	34.3	medium
Frontal cortex	tissue	34.2
Prostate	tissue	33.9	medium
Duodenum	tissue	33.8	medium
Kidney	tissue	33.7	medium
Cerebral cortex	tissue	33.1	medium
Occipital cortex	tissue	33.1
Urinary bladder	tissue	32.9	high
Salivary gland	tissue	32.7	medium
Lung	tissue	32.7	medium
Parathyroid gland	tissue	32.3	medium
Seminal vesicle	tissue	32.1	medium
Retrosplenial cortex	tissue	32.1
Somatosensory cortex	tissue	31.9
Retina	tissue	31.4
Fallopian tube	tissue	31.4	medium
Amygdala	tissue	31.0
Endometrium 1	tissue	30.9	medium
Rectum	tissue	30.5	medium
Small intestine	tissue	30.1	medium
Motor cortex	tissue	29.8
Adrenal gland	tissue	29.8	medium
Smooth muscle	tissue	29.4	medium
Cerebellum	tissue	28.8	high
Thyroid gland	tissue	28.7	medium
Basal ganglia	tissue	28.4	high
Retrosplenial and cingulate cortex	tissue	28.0

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (138.8), Dorsal spinal cord (111.4), Ventral spinal cord (109.8), Parieto-temporal junction (white matter) (88.1), Lateral funiculus (white matter) (86.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

Targeting FNTA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 44 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-584-3P	99.35	67.69	1082

Functional genomics

gnomAD constraint: pLI 0.00155, LOEUF 1.43, missense Z -1.26 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000302279 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:43,056,347–43,059,147	160 / 121.6	1.32	no
8:43,059,148–43,085,279	262 / 343.1	0.76	no
DepMap (CRISPR cell-line fitness): dependent in 90.7% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H1915 (-2.86), SCC-9 (-1.995), SK-N-FI (-1.763), MJ (-1.741), SW579 (-1.613), MPP 89 (-1.571), OCI-LY-19 (-1.528), HCC-78 (-1.522), G-402 (-1.51), DAN-G (-1.504), KMS-34 (-1.498), SNU-620 (-1.493), HUP-T4 (-1.445), C8166 (-1.435), SNU-668 (-1.392).

Literature-anchored findings (GeneRIF, showing 9)

• Results suggest that all peptide substrates adopt a common binding mode in the protein farnesyltransferase and geranylgeranyltransferase active site. (PMID:15451670)
• Geranylgeranyltransferase inhibitor-2147 (GGTI-2147), an inhibitor of protein prenylation, elicited significant inhibition of glucose-stimulated insulin secretion from INS 832/13 islet cells. (PMID:17192483)
• FTase, via its tubulin-association, is a critical upstream regulator of HDAC6 activity (PMID:19228685)
• our findings identify Geranylgeranyl transferase 1 as a key regulator of human airway smooth muscle cell viability (PMID:22160308)
• Exploring the putative self-binding property of the human farnesyltransferase alpha-subunit (PMID:28948621)
• These findings collectively suggest that the combination of farnesyltransferase inhibitors and gamma-secretase inhibitors is a promising therapeutic strategy for glioblastoma through selectively targeting the cancer stem cell subpopulation. (PMID:29198824)
• Cell-permeable CaaX-peptides affect K-Ras downstream signaling and promote cell death in cancer cells. (PMID:33112492)
• Scaffold association factor B (SAFB) is required for expression of prenyltransferases and RAS membrane association. (PMID:33257571)
• Protein farnesylation is upregulated in Alzheimer’s human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer’s model mice. (PMID:34315531)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fnta	ENSDARG00000099143
mus_musculus	Fnta	ENSMUSG00000015994
rattus_norvegicus	Fnta	ENSRNOG00000014462
drosophila_melanogaster	Fnta	FBGN0031633
caenorhabditis_elegans		WBGENE00019823

Paralogs (2): RABGGTA (ENSG00000100949), PTAR1 (ENSG00000188647)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104683) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal coat/hair pigmentation	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P29702	92.6%	Diamond
Lathyrus oleraceus	O24304	60.9%	Diamond
Arabidopsis thaliana	Q9LX33	60.9%	Diamond
Solanum lycopersicum	P93227	59.2%	Diamond
Schizosaccharomyces pombe 972h-	O60052	43.9%	Diamond
Dictyostelium discoideum	Q54RT9	43.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
HGSNAT	protein-coding	138050
POMK	protein-coding	84197
THAP1	protein-coding	55145
RNF170	protein-coding	81790
HOOK3	protein-coding	84376
MIR4469	ncRNA	100616115
CHRNA6	protein-coding	8973

Protein

Protein identifiers

Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha — P49354 (reviewed: P49354)

Alternative names: CAAX farnesyltransferase subunit alpha, FTase-alpha, Ras proteins prenyltransferase subunit alpha, Type I protein geranyl-geranyltransferase subunit alpha

All UniProt accessions (7): P49354, B3KVN2, E9PK84, E9PN85, E9PPM9, E9PQP6, H0YCW1

UniProt curated annotations — full annotation on UniProt →

Function. Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1 prenylation and activation.

Subunit / interactions. Heterodimer of FNTA and FNTB (farnesyltransferase). Heterodimer of FNTA and PGGT1B (geranylgeranyltransferase).

Post-translational modifications. Phosphorylated. Phosphorylation is mediated by MUSK upon AGRIN stimulation and results in the activation of FNTA.

Activity regulation. Activated by the AGRIN-induced phosphorylation which is mediated by MUSK.

Similarity. Belongs to the protein prenyltransferase subunit alpha family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49354-1	1	yes
P49354-2	2
P49354-3	3

RefSeq proteins (1): NP_002018* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002088	Prenyl_trans_a	Repeat

Pfam: PF01239

Enzyme classification (BRENDA)

• EC 2.5.1.58 — protein farnesyltransferase (BRENDA: 25 organisms, 389 substrates, 803 inhibitors, 111 Km, 113 kcat entries)
• EC 2.5.1.59 — protein geranylgeranyltransferase type I (BRENDA: 18 organisms, 93 substrates, 119 inhibitors, 28 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

131 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FARNESYL DIPHOSPHATE	—	9
GERANYLGERANYL DIPHOSPHATE	—	5
(2E,6E)-FARNESYL DIPHOSPHATE	0.0008–0.0015	3
DANSYL-GCVDS	0.003–0.011	3
YRASNRSCAIM	0.0003–0.003	3
(BIOTIN-CONH-(CH2)5-CO-)-NPFREKKFFCAI-LEU	0.0003–0.025	3
(2E,6E)-3,7-DIMETHYL-8-(PHENYLAMINO)OCTA-2,6-DIE	0.0004–0.0005	2
DANSYL-GCVKS	0.0014–0.01	2
DANSYL-GLY-CYS-LYS-THR-GLN	0.0005–0.0018	2
DANSYL-GLY-CYS-LYS-VAL-LEU	0.0007–0.0025	2
DANSYL-GLY-CYS-VAL-ILE-MET	0.0001–0.0002	2
DANSYL-GLY-CYS-VAL-LEU-SER	0.0007	2
DANSYL-GLY-CYS-ILE-ILE-LEU	0.0018–0.0024	2
RAS-CYS-VAL-LEU-LEU	0.0009–0.0012	2
(2E,6E)-3,7-DIMETHYL-8-(2,3,5,6-TETRAFLUOROPHENO	0.0512	1

Catalyzed reactions (Rhea)

• L-cysteinyl-[protein] + (2E,6E)-farnesyl diphosphate = S-(2E,6E)-farnesyl-L-cysteinyl-[protein] + diphosphate (RHEA:13345)
• geranylgeranyl diphosphate + L-cysteinyl-[protein] = S-geranylgeranyl-L-cysteinyl-[protein] + diphosphate (RHEA:21240)

UniProt features (43 total): helix 22, repeat 5, modified residue 3, initiator methionine 2, splice variant 2, mutagenesis site 2, turn 2, chain 1, sequence conflict 1, strand 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

14 structures by resolution:

PDB	Title	Method	Resolution (Å)
2H6F	Protein Farnesyltransferase Complexed with a Farnesylated DDPTASACVLS Peptide Product at …	X-RAY DIFFRACTION	1.5
1LD8	Co-crystal structure of Human Farnesyltransferase with farnesyldiphosphate and inhibitor …	X-RAY DIFFRACTION	1.8
1TN6	Protein Farnesyltransferase Complexed with a Rap2a Peptide Substrate and a FPP Analog at …	X-RAY DIFFRACTION	1.8
2H6H	Y365F Protein Farnesyltransferase Mutant Complexed with a Farnesylated DDPTASACVLS …	X-RAY DIFFRACTION	1.8
2IEJ	Human Protein Farnesyltransferase Complexed with Inhibitor Compound STN-48 And FPP Analog …	X-RAY DIFFRACTION	1.8
3E37	Protein farnesyltransferase complexed with bisubstrate ethylenediamine scaffold inhibitor …	X-RAY DIFFRACTION	1.8
2H6G	W102T Protein Farnesyltransferase Mutant Complexed with a Geranylgeranylated DDPTASACVLS …	X-RAY DIFFRACTION	1.85
1S63	Human protein farnesyltransferase complexed with L-778,123 and FPP	X-RAY DIFFRACTION	1.9
1LD7	Co-crystal structure of Human Farnesyltransferase with farnesyldiphosphate and inhibitor …	X-RAY DIFFRACTION	2
1MZC	Co-Crystal Structure Of Human Farnesyltransferase With Farnesyldiphosphate and Inhibitor …	X-RAY DIFFRACTION	2
1SA4	human protein farnesyltransferase complexed with FPP and R115777	X-RAY DIFFRACTION	2.1
1JCQ	CRYSTAL STRUCTURE OF HUMAN PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYL …	X-RAY DIFFRACTION	2.3
2F0Y	Crystal Structure Of Human Protein Farnesyltransferase Complexed With Farnesyl …	X-RAY DIFFRACTION	2.7
2H6I	W102T/Y365F Protein Farnesyltransferase Double Mutant Complexed with a Geranylgeranylated …	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49354-F1	89.12	0.84

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, FDA approved drug targets, Small molecule drugs, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3)

Type	Positions
Phosphoserine	373
N-acetylalanine	2, 2

Mutagenesis-validated functional residues (2)

Position	Phenotype
164	reduced activity.
199	reduced catalytic efficiency.

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 19; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

19 pathways:

ID	Pathway	Evidence
R-HSA-9679191	Potential therapeutics for SARS ⚕	curated
R-HSA-111465	Apoptotic cleavage of cellular proteins	curated
R-HSA-9953170	GBP-mediated host defense	curated
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade	curated
R-HSA-9648002	RAS processing	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-109581	Apoptosis	—
R-HSA-75153	Apoptotic execution phase	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-5673001	RAF/MAP kinase cascade	—
R-HSA-9709957	Sensory Perception	—
R-HSA-162582	Signal Transduction	—
R-HSA-2514856	The phototransduction cascade	—
R-HSA-2187338	Visual phototransduction	—

MSigDB gene sets: 215 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TTTGTAG_MIR520D, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, HSIAO_HOUSEKEEPING_GENES, CAFFAREL_RESPONSE_TO_THC_UP, GOBP_PROTEIN_MATURATION, GOBP_CELL_JUNCTION_ORGANIZATION, MARTINEZ_RB1_TARGETS_DN, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOBP_REGULATION_OF_RAC_PROTEIN_SIGNAL_TRANSDUCTION

GO Biological Process (11): transforming growth factor beta receptor signaling pathway (GO:0007179), peptide pheromone maturation (GO:0007323), protein farnesylation (GO:0018343), protein geranylgeranylation (GO:0018344), positive regulation of Rac protein signal transduction (GO:0035022), regulation of microtubule-based movement (GO:0060632), skeletal muscle acetylcholine-gated channel clustering (GO:0071340), CAAX-box protein maturation (GO:0080120), enzyme-linked receptor protein signaling pathway (GO:0007167), neuromuscular junction development (GO:0007528), protein prenylation (GO:0018342)

GO Molecular Function (14): protein farnesyltransferase activity (GO:0004660), protein geranylgeranyltransferase activity (GO:0004661), CAAX-protein geranylgeranyltransferase activity (GO:0004662), Rab geranylgeranyltransferase activity (GO:0004663), microtubule binding (GO:0008017), acetyltransferase activator activity (GO:0010698), enzyme binding (GO:0019899), receptor tyrosine kinase binding (GO:0030971), alpha-tubulin binding (GO:0043014), molecular adaptor activity (GO:0060090), prenyltransferase activity (GO:0004659), protein binding (GO:0005515), protein prenyltransferase activity (GO:0008318), transferase activity (GO:0016740)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule associated complex (GO:0005875), plasma membrane (GO:0005886), CAAX-protein geranylgeranyltransferase complex (GO:0005953), protein farnesyltransferase complex (GO:0005965)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Apoptotic execution phase	1
The phototransduction cascade	1
RAF/MAP kinase cascade	1
SARS-CoV Infections	1
Antimicrobial mechanism of IFN-stimulated genes	1
Programmed Cell Death	1
Sensory Perception	1
Visual phototransduction	1
Disease	1
MAPK1/MAPK3 signaling	1
Signal Transduction	1
MAPK family signaling cascades	1
Apoptosis	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

40 GO namespaces:

Category	Terms
protein prenylation	3
protein maturation	2
protein prenyltransferase activity	2
protein geranylgeranyltransferase activity	2
tubulin binding	2
binding	2
cellular anatomical structure	2
cytoplasm	2
transferase complex	2
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
microtubule-based movement	1
regulation of microtubule-based process	1
postsynaptic membrane organization	1
neuromuscular junction development	1
receptor clustering	1
protein processing	1
cell surface receptor signaling pathway	1
synapse organization	1
protein modification process	1
prenylation	1
enzyme activator activity	1
acetyltransferase activity	1
protein binding	1
signaling receptor binding	1
protein tyrosine kinase binding	1
molecular_function	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
prenyltransferase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
protein-containing complex	1
membrane	1
cell periphery	1
intracellular protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
protein farnesylation	BP	direct assay
protein geranylgeranylation	BP	direct assay
regulation of microtubule-based movement	BP	direct assay
CAAX-protein geranylgeranyltransferase complex	CC	direct assay
microtubule associated complex	CC	direct assay
protein farnesyltransferase complex	CC	direct assay
acetyltransferase activator activity	MF	direct assay
alpha-tubulin binding	MF	direct assay
enzyme binding	MF	physical interaction
microtubule binding	MF	direct assay
molecular adaptor activity	MF	experiment
protein farnesyltransferase activity	MF	direct assay
protein geranylgeranyltransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 890 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FNTA	PGGT1B	P53609	971
FNTA	FNTB	P49356	959
FNTA	RABGGTB	P53611	851
FNTA	B4DL54	B4DL54	768
FNTA	TPT1	P13693	661
FNTA	ICMT	O60725	627
FNTA	RPS6KB2	Q9UBS0	609
FNTA	RCE1	Q9Y256	600
FNTA	DHDDS	Q86SQ9	567
FNTA	ZMPSTE24	O75844	538
FNTA	FKBP8	Q14318	497
FNTA	FDFT1	P37268	496
FNTA	PTAR1	Q7Z6K3	493
FNTA	FDPS	P14324	491
FNTA	POMK	Q9H5K3	486

IntAct

Human interaction partners of FNTA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
FNTB	direct interaction	0.960	13
PGGT1B	physical association	0.840	7
AP4M1	physical association	0.560	3
KRAS	physical association	0.560	3
HRAS	physical association	0.560	1
NRAS	physical association	0.560	1
AMMECR1L	association	0.530	2
RAP1B	physical association	0.400	1
RAP2A	physical association	0.400	1
CFTR	physical association	0.370	1
INHBB	physical association	0.370	1
RPL13A	physical association	0.370	1
SAFB2	physical association	0.370	1
STAT2	physical association	0.370	1
TGM2	physical association	0.370	1
YKT6	association	0.350	2
ARNT2	association	0.350	1
CEFIP	association	0.350	1
CHURC1-FNTB	association	0.350	1
FBXL2	association	0.350	1
PPIF	association	0.350	1
SDCBP	association	0.350	1
TP53TG5	association	0.350	1
VPS37C	association	0.350	1
PTP4A2	physical association	0.000	1
PTP4A3	physical association	0.000	1
VAV2	physical association	0.000	1

BioGRID (126 interactions; top human partners by supporting records): FNTB (Affinity Capture-MS; 7 records), DYRK1A (Affinity Capture-MS; 6 records), AMMECR1L (Affinity Capture-MS; 3 records), HDAC6 (Co-fractionation; 3 records), HEYL (Affinity Capture-MS; 3 records), NAP1L1 (Affinity Capture-MS; 3 records), PGGT1B (Two-hybrid; 3 records), PTP4A2 (Affinity Capture-MS; 3 records), TGFBR1 (Two-hybrid; 3 records), ARFGAP1 (Affinity Capture-MS; 2 records), ARNT2 (Affinity Capture-MS; 2 records), C10orf71 (Affinity Capture-MS; 2 records), CAPN1 (Affinity Capture-MS; 2 records), EPB41L5 (Affinity Capture-MS; 2 records), FAM117B (Affinity Capture-MS; 2 records)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
TP53	“up-regulates quantity by expression”	FNTA	“transcriptional regulation”
FNTA	“up-regulates activity”	MRAS
FNTA	“up-regulates activity”	KRAS
FNTA	“up-regulates activity”	HRAS
tipifarnib	“down-regulates activity”	FNTA	“chemical inhibition”

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ Protein geranylgeranyltransferase type-1 complex	2	FNTA, PGGT1B
★ Protein farnesyltransferase complex	2	FNTA, FNTB

Disease & clinical

Genetic variants

Variant evidence for FNTA: 75 ClinVar records (1 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

75 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4070977	NM_002027.3(FNTA):c.863del (p.Gly288fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore FNTA’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 45 predictions of 690):

Position(s)	Effect	Δscore	Sites
8:43069553–43069554	acceptor_loss	1.0000	6
8:43069660–43069661	donor_loss	1.0000	5
8:43072171	acceptor_gain	1.0000
8:43072179–43072180	acceptor_loss	1.0000	4
8:43084709	acceptor_loss	1.0000	2
8:43084882–43084883	donor_loss	1.0000	5
8:43056547–43056548	donor_loss	0.9900	5
8:43059178–43059179	donor_loss	0.9900	6
8:43064099–43064100	acceptor_loss	0.9900	6
8:43064216–43064217	donor_loss	0.9900	5

AlphaMissense

1,189 missense substitutions predicted likely pathogenic (of 2,517 scored), across 256 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D196	8	0.999	1.000
H201	8	0.999	1.000
D349	8	0.999	1.000
N199	8	0.998	1.000
D230	8	0.997	0.999
H171	8	0.996	1.000
N233	8	0.996	1.000
N165	8	0.995	1.000
N234	8	0.995	1.000
N273	8	0.991	1.000
D98	8	0.987	0.997
N127	8	0.984	1.000
D317	8	0.981	0.994
F96	8	0.973	1.000
N238	8	0.968	0.999
S275	8	0.964	1.000
H170	8	0.955	0.999
F188	8	0.953	0.998
N130	8	0.952	1.000
F103	8	0.943	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	1.07e-05
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	2.27e-05

Disease associations

OMIM: gene MIM:134635 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): hypercholesterolemia, familial, 1 (MONDO:0007750)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

GWAS associations

1 associations:

Study	Trait	p-value
GCST002934_2	Zinc levels	6e-7

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2094108 (PROTEIN COMPLEX), CHEMBL2095164 (PROTEIN COMPLEX), CHEMBL2096991 (PROTEIN COMPLEX GROUP), CHEMBL271 (SINGLE PROTEIN)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes FNTA — the drug acts on the assembly or class, not necessarily on this subunit alone.

2 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
LONAFARNIB	Protein farnesyltransferase	2	4
TIPIFARNIB	Protein farnesyltransferase	2	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 49,019 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

6 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1650	CORTISONE ACETATE	4	16,069
CHEMBL298734	LONAFARNIB	4	13,020
CHEMBL289228	TIPIFARNIB	3	19,147
CHEMBL351706	BMS-214662	1	403
CHEMBL3218390	GGTI-2418	1	39
CHEMBL279433	L-778123 FREE BASE	1	341

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Protein farnesyltransferase

Binding affinities (BindingDB)

1191 measured of 1344 human assays (1471 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
6-({[3-(4-Cyano-benzyl)-3H-imidazol-4-ylmethyl]-amino}-methyl)-3’’-ethoxy-biphenyl-3-carbonitrile	IC50	0.01 nM
6-({[3-(4-Cyano-benzyl)-3H-imidazol-4-ylmethyl]-methyl-amino}-methyl)-3’’-ethoxy-biphenyl-3-carbonitrile	IC50	0.03 nM
4-[(S)-1-Amino-1-(3-methyl-3H-imidazol-4-yl)-ethyl]-2-[3-((S)-3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-benzonitrile	IC50	0.06 nM
CHEMBL4565280	IC50	0.06 nM
Lithium; (S)-2-({5-[5-(4-chloro-phenyl)-furan-2-ylmethoxymethyl]-2’-methyl-biphenyl-2-carbonyl}-amino)-4-methylsulfanyl-butyrate	EC50	0.1 nM
3-Benzo[1,3]dioxol-5-yl-4-[3-(4-cyano-benzyl)-3H-imidazol-4-ylmethoxymethyl]-benzonitrile	IC50	0.1 nM
4-(3-bromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-piperazine-1,2-dicarboxylicacid 1-cyclohexylamide 2-[(3-imidazol-1-yl-propyl)-amide]	IC50	0.1 nM
CHEMBL3115256	IC50	0.1 nM
CHEMBL3115255	IC50	0.1 nM
(S)-2-[(5-{2-[4-(Adamantane-1-carbonyl)-pyridin-3-yl]-vinyl}-2’-methyl-biphenyl-2-carbonyl)-amino]-4-methylsulfanyl-butyric acid	IC50	0.12 nM
(S)-2-(2-{[(S)-2-((R)-2-Amino-3-mercapto-propylamino)-3-methyl-pentyl]-naphthalen-1-ylmethyl-amino}-acetylamino)-4-methylsulfanyl-butyric acid	IC50	0.123 nM
(S)-2-({5-[2-(3H-Imidazol-4-yl)-ethyl]-2’-methyl-biphenyl-2-carbonyl}-amino)-4-methylsulfanyl-butyric acid	IC50	0.15 nM
CHEMBL252953	IC50	0.15 nM
4-{5-[(S)-4-(3-Chloro-phenyl)-2-ethanesulfonylmethyl-5-oxo-piperazin-1-ylmethyl]-imidazol-1-ylmethyl}-benzonitrile	IC50	0.18 nM
(S)-2-{[5-(2-Imidazol-1-yl-vinyl)-2’-methyl-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyric acid	IC50	0.2 nM
4-[3-(4-Cyano-benzyl)-3H-imidazol-4-ylmethyl]-piperazine-1-carboxylic acid adamantan-1-ylamide	IC50	0.2 nM
3-oxo-18-oxa-2,5,9,11-tetraazahexacyclo[17.6.2.22,5.113,17.07,11.022,26]triaconta-1(26),7,9,13(30),14,16,19(27),20,22,24-decaen-16-yl cyanide	IC50	0.2 nM
CHEMBL3115258	IC50	0.2 nM
(S)-2-{[5-(2-Imidazol-1-yl-ethyl)-2’-methyl-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyric acid	IC50	0.21 nM
6-[3-(4-Cyano-benzyl)-3H-imidazol-4-ylmethoxymethyl]-3’’-ethoxy-biphenyl-3-carbonitrile	IC50	0.27 nM
(S)-2-({5-[2-((E)-4-Chloro-pyridin-3-yl)-vinyl]-2’-methyl-biphenyl-2-carbonyl}-amino)-4-methylsulfanyl-butyric acid	IC50	0.29 nM
(S)-2-({5-[2-((E)-4-Hydroxy-pyridin-3-yl)-vinyl]-2’-methyl-biphenyl-2-carbonyl}-amino)-4-methylsulfanyl-butyric acid	IC50	0.29 nM
(S)-2-[(5-{2-[(E)-4-(3,5-Difluoro-benzyloxy)-pyridin-3-yl]-vinyl}-2’-methyl-biphenyl-2-carbonyl)-amino]-4-methylsulfanyl-butyric acid	IC50	0.3 nM
Lithium; (S)-2-{[2’-methyl-5-(5-pyridin-3-yl-furan-2-ylmethoxymethyl)-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyrate	EC50	0.3 nM
N-[3-(4-Cyano-benzyl)-3H-imidazol-4-ylmethyl]-N-(5-cyano-3’’-ethoxy-biphenyl-2-ylmethyl)-acetamide	IC50	0.31 nM
4-[3-(4-Cyano-benzyl)-3H-imidazol-4-ylmethyl]-piperazine-1-carboxylic acid 2-methoxymethyl-benzyl ester	IC50	0.32 nM
4’’-tert-Butyl-6-[3-(4-cyano-benzyl)-3H-imidazol-4-ylmethoxymethyl]-biphenyl-3-carbonitrile	IC50	0.36 nM
(S)-2-[(5-{2-[4-(Adamantan-1-yl-hydroxy-methyl)-pyridin-3-yl]-vinyl}-2’-methyl-biphenyl-2-carbonyl)-amino]-4-methylsulfanyl-butyric acid	IC50	0.37 nM
6-[3-(4-Cyano-phenyl)-3-hydroxy-3-(3-methyl-3H-imidazol-4-yl)-prop-1-ynyl]-3’’-methoxy-biphenyl-3-carbonitrile	IC50	0.37 nM
3’’-Chloro-6-[3-(4-cyano-benzyl)-3H-imidazol-4-ylmethoxymethyl]-biphenyl-3-carbonitrile	IC50	0.37 nM
6-(((1-(4-cyanobenzyl)-1H-imidazol-5-yl)methoxy)methyl)-3’-(trifluoromethoxy)biphenyl-3-carbonitrile	IC50	0.37 nM
CHEMBL3115265	IC50	0.4 nM
CHEMBL3218392	IC50	0.4 nM
(S)-2-[3-({(4-Cyano-benzyl)-[3-(4-cyano-benzyl)-3H-imidazol-4-ylmethyl]-amino}-methyl)-benzoylamino]-4-methylsulfanyl-butyric acid	IC50	0.41 nM
4-{5-[(S)-2-Butyl-4-(2,3-dimethyl-phenyl)-5-oxo-piperazin-1-ylmethyl]-imidazol-1-ylmethyl}-benzonitrile	IC50	0.44 nM
(R)-2-({(S)-2-[(S)-2-((R)-2-Amino-3-mercapto-propylamino)-3,3-dimethyl-butyryl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-4-methanesulfonyl-butyric acid	IC50	0.46 nM
6-[3-(4-Cyano-benzyl)-3H-imidazol-4-ylmethoxymethyl]-3’’-methoxy-biphenyl-3-carbonitrile	IC50	0.46 nM
2-{[5-((R)-2-Amino-3-mercapto-propylamino)-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyric acid	IC50	0.5 nM
(S)-2-[(5-{2-[(E)-4-(Cyclohexyl-hydroxy-methyl)-pyridin-3-yl]-vinyl}-2’-methyl-biphenyl-2-carbonyl)-amino]-4-methylsulfanyl-butyric acid	IC50	0.54 nM
(R)-2-({(S)-2-[(S)-2-((R)-2-Amino-3-mercapto-propylamino)-3,3-dimethyl-butyryl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-4-methylsulfanyl-butyric acid	IC50	0.57 nM
(S)-2-[(5-{2-[(E)-4-(Hydroxy-phenyl-methyl)-pyridin-3-yl]-vinyl}-2’-methyl-biphenyl-2-carbonyl)-amino]-4-methylsulfanyl-butyric acid	IC50	0.58 nM
(S)-2-{[5-((Z)-1-Cyano-2-pyridin-3-yl-vinyl)-2’-methyl-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyric acid	IC50	0.59 nM
(R)-2-({(R)-2-[(R)-2-((S)-2-Amino-3-mercapto-propylamino)-3-methyl-butyryl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-4-methylsulfanyl-butyric acid	IC50	0.6 nM
(S)-2-({2-[(S)-2-((R)-2-Amino-3-mercapto-propylamino)-3-methyl-butyryl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-4-methylsulfanyl-butyric acid	IC50	0.6 nM
6-{3-[3-(4-Cyano-benzyl)-3H-imidazol-4-yl]-3-hydroxy-prop-1-ynyl}-3’’-ethoxy-biphenyl-3-carbonitrile	IC50	0.6 nM
N-(6-cyano-1-((1-methyl-1H-imidazol-5-yl)methyl)-1,2,3,4-tetrahydroquinolin-3-yl)-1-methyl-N-(thiophen-3-ylmethyl)-1H-imidazole-4-sulfonamide	IC50	0.6 nM
CHEMBL3115429	IC50	0.6 nM
CHEMBL3115426	IC50	0.6 nM
CHEMBL3115261	IC50	0.6 nM
(S)-2-({2’-Methyl-5-[((E)-2-pyridin-3-yl)-vinyl]-biphenyl-2-carbonyl}-amino)-4-methylsulfanyl-butyric acid	IC50	0.61 nM

ChEMBL bioactivities

2679 potent at pChembl≥5 of 3016 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL361246
10.70	IC50	0.02	nM	(1R,5R)-30-OXO-19-OXA-2,6,10,12-TETRAAZAHEXACYCLO[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]TRIACONTA-8,10,14(29),15,17,20(28),21,23(27)-OCTAENE-17-CARBONITRILE (STRUCTURAL MIX)
10.52	IC50	0.03	nM	CHEMBL426063
10.44	IC50	0.036	nM	CHEMBL128501
10.22	IC50	0.06	nM	CHEMBL310586
10.22	IC50	0.06	nM	CHEMBL294888
10.22	IC50	0.06	nM	CHEMBL4565280
10.10	IC50	0.079	nM	CHEMBL23578
10.10	IC50	0.08	nM	CHEMBL379900
10.05	IC50	0.09	nM	CHEMBL378462
10.00	IC50	0.1	nM	CHEMBL52073
10.00	EC50	0.1	nM	CHEMBL10877
10.00	EC50	0.1	nM	CHEMBL24043
10.00	IC50	0.1	nM	CHEMBL3115256
10.00	IC50	0.1	nM	CHEMBL3115255
10.00	IC50	0.1	nM	CHEMBL364792
10.00	IC50	0.1	nM	CHEMBL381360
10.00	IC50	0.1	nM	CHEMBL160223
9.96	IC50	0.11	nM	CHEMBL125162
9.92	EC50	0.12	nM	CHEMBL516874
9.92	IC50	0.12	nM	CHEMBL436440
9.92	IC50	0.12	nM	CHEMBL327106
9.92	IC50	0.12	nM	CHEMBL321252
9.92	IC50	0.12	nM	CHEMBL99901
9.91	IC50	0.123	nM	CHEMBL112189
9.91	IC50	0.123	nM	CHEMBL1790750
9.85	EC50	0.14	nM	CHEMBL399482
9.82	IC50	0.15	nM	CHEMBL526466
9.82	IC50	0.15	nM	CHEMBL163383
9.82	IC50	0.15	nM	CHEMBL252953
9.82	IC50	0.15	nM	CHEMBL322355
9.80	IC50	0.16	nM	CHEMBL438264
9.80	IC50	0.16	nM	CHEMBL324081
9.80	IC50	0.16	nM	CHEMBL64183
9.74	EC50	0.18	nM	(1R,5R)-30-OXO-19-OXA-2,6,10,12-TETRAAZAHEXACYCLO[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]TRIACONTA-8,10,14(29),15,17,20(28),21,23(27)-OCTAENE-17-CARBONITRILE (STRUCTURAL MIX)
9.74	IC50	0.18	nM	CHEMBL125558
9.74	EC50	0.18	nM	CHEMBL442552
9.74	IC50	0.18	nM	CHEMBL322435
9.72	IC50	0.19	nM	CHEMBL80702
9.72	IC50	0.19	nM	CHEMBL329932
9.72	EC50	0.19	nM	CHEMBL435247
9.72	IC50	0.19	nM	CHEMBL316673
9.70	IC50	0.2	nM	CHEMBL3115258
9.70	IC50	0.2	nM	CHEMBL377974
9.70	IC50	0.2	nM	CHEMBL424564
9.70	IC50	0.2	nM	CHEMBL159400
9.70	IC50	0.2	nM	CHEMBL52073
9.68	IC50	0.21	nM	CHEMBL205973
9.68	IC50	0.21	nM	CHEMBL159764
9.62	IC50	0.24	nM	CHEMBL380313

PubChem BioAssay actives

2659 with measured affinity, of 4293 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1R,5R)-30-oxo-19-oxa-2,6,10,12-tetrazahexacyclo[18.6.2.12,5.114,18.08,12.023,27]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	1121277: Inhibition of human recombinant FTase using [3H]farnesyldiphosphate	ic50	<0.0001	uM
4-[[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methylamino]methyl]-3-(3-ethoxyphenyl)benzonitrile	242407: Inhibition of [3H]FPP incorporation into recombinant Ras CVIM by human Farnesyltransferase	ic50	<0.0001	uM
5-(3-chlorophenyl)-6-[[(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]-2-oxo-1-propylpyridine-3-carbonitrile	71312: In vitro inhibitory activity against farnesyltransferase (FT)	ic50	<0.0001	uM
4-[[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl-methylamino]methyl]-3-(3-ethoxyphenyl)benzonitrile	242407: Inhibition of [3H]FPP incorporation into recombinant Ras CVIM by human Farnesyltransferase	ic50	<0.0001	uM
4-[[5-[[(2S)-2-butyl-4-(3-chlorophenyl)-5-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile	73130: Inhibition of [3H]FPP incorporation into recombinant human K-Ras by Farnesyltransferase	ic50	0.0001	uM
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3S)-3-butyl-1-methyl-2-oxoazepan-3-yl]phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0001	uM
4-[[(R)-(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]-3-(3-methoxyphenyl)benzonitrile	143977: Effective concentration required for inhibition of farnesylation of Ras protein in NIH3T3 cells	ec50	0.0001	uM
3-(1,3-benzodioxol-5-yl)-4-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methoxymethyl]benzonitrile	242407: Inhibition of [3H]FPP incorporation into recombinant Ras CVIM by human Farnesyltransferase	ic50	0.0001	uM
155543825	1585808: Inhibition of human recombinant FTase using [3H]FPP as substrate after 15 mins by scintillation counting analysis	ic50	0.0001	uM
5-[[3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-yl-2,4-dioxoimidazolidin-1-yl]methyl]-2-methylsulfanylbenzonitrile	263454: Inhibition of farnesyl transferase	ic50	0.0001	uM
23-oxo-4-prop-2-enyl-8-oxa-1,15,17,21-tetrazapentacyclo[19.2.2.13,7.19,13.015,19]heptacosa-3,5,7(27),9,11,13(26),16,18-octaene-10-carbonitrile	73548: Inhibition of human Farnesyltransferase -catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0001	uM
3-[[3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-yl-2,4-dioxoimidazolidin-1-yl]methyl]benzonitrile	263454: Inhibition of farnesyl transferase	ic50	0.0001	uM
lithium (2S)-2-[[4-[[5-(4-chlorophenyl)furan-2-yl]methoxymethyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoate	72945: EC50 is measured as inhibition of ras processing in a whole cell assay for farnesyltransferase (FTase)	ec50	0.0001	uM
32-oxo-25-oxa-8,12,16,18-tetrazahexacyclo[24.3.1.18,11.120,24.02,7.014,18]dotriaconta-1(30),2,4,6,14,16,20(31),21,23,26,28-undecaene-23-carbonitrile	73277: Inhibition of Farnesyltransferase in PSN-1 cells at 10 pM	ic50	0.0001	uM
(2S)-2-[[2-[[(2S)-2-[[(2R)-2-amino-3-sulfanylpropyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	168708: Inhibition of [3H]- FPP incorporation into recombinant Ha-Ras by farnesyl transferase at 10 pM	ic50	0.0001	uM
(2S)-2-[[2-[[(2S)-3-methyl-2-[[2-[3-(naphthalen-2-ylmethyl)imidazol-4-yl]acetyl]amino]pentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73432: Inhibition of [3H]FPP incorporation into recombinant [Leu68]-RAS1CVIM by Farnesyltransferase	ic50	0.0001	uM
(2S)-2-[[2-[[(2S)-3-methyl-2-[[2-[3-(naphthalen-1-ylmethyl)imidazol-4-yl]acetyl]amino]pentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73432: Inhibition of [3H]FPP incorporation into recombinant [Leu68]-RAS1CVIM by Farnesyltransferase	ic50	0.0001	uM
(2S)-2-[[2-[[(2S)-2-[[2-(3-benzylimidazol-4-yl)acetyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73544: Inhibition of [3H]FPP incorporation into recombinant [Leu68]-RAS1CVIM by Farnesyltransferase	ic50	0.0001	uM
(2S)-2-[[4-[2-(1H-imidazol-5-yl)ethyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid	73125: Inhibitory activity against farnesyltransferase (FT) using SPA assay	ic50	0.0001	uM
(2S)-2-[[4-[(E)-2-[4-(adamantane-1-carbonyl)-3-pyridinyl]ethenyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid	73125: Inhibitory activity against farnesyltransferase (FT) using SPA assay	ic50	0.0001	uM
4-(6-bromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl)-1-N-cyclohexyl-2-N-(3-imidazol-1-ylpropyl)piperazine-1,2-dicarboxamide	259952: Inhibitory activity against Farnesyltransferase quantified by modified SPA assay with improved sensitivity	ic50	0.0001	uM
(2S)-2-[[2-[[(2S,3R)-2-[[2-[3-[(4-cyanophenyl)methyl]imidazol-4-yl]acetyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73400: Inhibitory concentration against farnesyltransferase was determined	ic50	0.0001	uM
4-[3-(4-cyanophenyl)-3-hydroxy-3-(3-methylimidazol-4-yl)prop-1-ynyl]-3-(3-ethoxyphenyl)benzonitrile	144106: Inhibition of farnesylation in NIH-3T3H-ras cell line	ec50	0.0001	uM
4-[1-hydroxy-3-[2-(3-methoxyphenyl)-4-pentanoylphenyl]-1-(3-methylimidazol-4-yl)prop-2-ynyl]benzonitrile	144106: Inhibition of farnesylation in NIH-3T3H-ras cell line	ec50	0.0001	uM
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3S)-3-ethyl-1-methyl-2-oxoazepan-3-yl]phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0001	uM
(2S)-2-[[2-[[(2S,3R)-2-[[(2R)-2-amino-3-sulfanylpropyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-hydroxybutanoic acid	73128: Inhibition of [3H]FPP incorporation into recombinant human Ha-Ras by Farnesyltransferase	ic50	0.0001	uM
4-[(2S)-13-chloro-10-[(1S)-1-hydroxy-1-(3-methylimidazol-4-yl)ethyl]-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-yl]-N-cyclohexylpiperazine-1-carboxamide	1070173: Inhibition of FTase (unknown origin) assessed as transfer of [H3]farnesyl from [H3]farnesyl pyrophosphate to trichloroacetic acid-precipitable HaRas-CVLS	ic50	0.0001	uM
4-[(2S)-13-chloro-10-[(1S)-1-hydroxy-1-(3-methylimidazol-4-yl)ethyl]-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-yl]piperazine-1-carboxamide	1070173: Inhibition of FTase (unknown origin) assessed as transfer of [H3]farnesyl from [H3]farnesyl pyrophosphate to trichloroacetic acid-precipitable HaRas-CVLS	ic50	0.0001	uM
(1R,5R)-29-oxo-19-oxa-2,6,10,12-tetrazahexacyclo[18.5.2.12,5.114,18.08,12.023,26]nonacosa-8,10,14(28),15,17,20(27),21,23(26)-octaene-17-carbonitrile	73276: Inhibition of Farnesyltransferase in PSN-1 cells at 10 pM	ic50	0.0001	uM
(1R,5R)-30-oxo-19,24-dioxa-2,6,10,12-tetrazahexacyclo[18.6.2.12,5.114,18.08,12.023,27]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	81892: Inhibition of HDJ2 farnesylation in PSN-1 cells over 7 hr assay	ec50	0.0001	uM
3-oxo-18-oxa-2,5,9,11-tetrazahexacyclo[17.6.2.22,5.113,17.07,11.022,26]triaconta-1(25),7,9,13(28),14,16,19(27),20,22(26),23-decaene-16-carbonitrile	73274: In vitro inhibitory activity to reduce the human farnesyltransferase catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM	ic50	0.0001	uM
4-[3-(4-cyanophenyl)-3-hydroxy-3-(3-methylimidazol-4-yl)prop-1-ynyl]-3-(3,5-dichlorophenyl)benzonitrile	72822: Inhibition of human FTase-catalyzed incorporation of [3H]FPP into recombinant Ras CVIM	ic50	0.0001	uM
4-[[(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]-3-(3-ethoxyphenyl)benzonitrile	143977: Effective concentration required for inhibition of farnesylation of Ras protein in NIH3T3 cells	ec50	0.0002	uM
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3R)-3-(2-cyclopropylethyl)-1-methyl-2-oxoazepan-3-yl]phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0002	uM
4-[(1S)-1-amino-1-(3-methylimidazol-4-yl)ethyl]-2-[3-[(3R)-1-methyl-2-oxo-3-(3,3,3-trifluoropropyl)azepan-3-yl]phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0002	uM
4-[[(4-cyanophenyl)-(3-methylimidazol-4-yl)methoxy]methyl]-3-[3-(methoxymethyl)phenyl]benzonitrile	1797019: Enzyme Inhibition Assay from Article 10.1021/jm030434f: “Design, synthesis, and biological activity of 4-[(4-cyano-2-arylbenzyloxy)-(3-methyl-3H-imidazol-4-yl)methyl]benzonitriles as potent and selective farnesyltransferase inhibitors.”	ic50	0.0002	uM
4-[amino-(3-methylimidazol-4-yl)methyl]-2-[3-(3-ethyl-1-methyl-2-oxoazepan-3-yl)phenoxy]benzonitrile	73259: Concentration required to inhibit recombinant human farnesyltransferase (FTase) catalyzed incorporation of [3H]FPP into recombinant Ras-CVIM.	ic50	0.0002	uM
31-oxo-20-oxa-2,6,11,13-tetrazahexacyclo[19.6.2.12,5.115,19.09,13.024,28]hentriaconta-1(27),9,11,15(30),16,18,21(29),22,24(28),25-decaene-18-carbonitrile	73276: Inhibition of Farnesyltransferase in PSN-1 cells at 10 pM	ic50	0.0002	uM
(2S)-2-[[4-(2-imidazol-1-ylethyl)-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid	73125: Inhibitory activity against farnesyltransferase (FT) using SPA assay	ic50	0.0002	uM
4-[[3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-yl-2,4-dioxoimidazolidin-1-yl]methyl]benzoic acid	263454: Inhibition of farnesyl transferase	ic50	0.0002	uM
3-(3-imidazol-1-ylpropyl)-5-methyl-1-[[4-(methylsulfanylmethyl)phenyl]methyl]-5-naphthalen-1-ylimidazolidine-2,4-dione	263454: Inhibition of farnesyl transferase	ic50	0.0002	uM
1-[(4-bromophenyl)methyl]-3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-ylimidazolidine-2,4-dione	263454: Inhibition of farnesyl transferase	ic50	0.0002	uM
1-[(3-chlorophenyl)methyl]-3-(3-imidazol-1-ylpropyl)-5-methyl-5-naphthalen-1-ylimidazolidine-2,4-dione	263454: Inhibition of farnesyl transferase	ic50	0.0002	uM
(1R)-30-oxo-19-oxa-2,6,10,12-tetrazahexacyclo[18.6.2.12,5.114,18.08,12.023,27]triaconta-8,10,14(29),15,17,20(28),21,23(27)-octaene-17-carbonitrile	157058: Effective concentration required to inhibit HDJ2 farnesylation in PSN-1 cells	ec50	0.0002	uM
(2S)-2-[[2-[[(2S)-3-methyl-2-[[2-[3-[(4-nitrophenyl)methyl]imidazol-4-yl]acetyl]amino]pentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid	73544: Inhibition of [3H]FPP incorporation into recombinant [Leu68]-RAS1CVIM by Farnesyltransferase	ic50	0.0002	uM
4-[[5-[[(2S)-4-(3-chlorophenyl)-2-(ethylsulfonylmethyl)-5-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile	73130: Inhibition of [3H]FPP incorporation into recombinant human K-Ras by Farnesyltransferase	ic50	0.0002	uM
propan-2-yl 4-[(2S)-13-chloro-10-[(1S)-1-hydroxy-1-(3-methylimidazol-4-yl)ethyl]-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-yl]piperazine-1-carboxylate	1070173: Inhibition of FTase (unknown origin) assessed as transfer of [H3]farnesyl from [H3]farnesyl pyrophosphate to trichloroacetic acid-precipitable HaRas-CVLS	ic50	0.0002	uM
N-(1-adamantyl)-4-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl]piperazine-1-carboxamide	74653: Inhibitory activity against human Geranylgeranyl transferase type I	ic50	0.0002	uM
(2S)-2-[[4-[(E)-2-imidazol-1-ylethenyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid	73125: Inhibitory activity against farnesyltransferase (FT) using SPA assay	ic50	0.0002	uM
[2-(trifluoromethoxy)phenyl]methyl 4-[[3-[(4-cyanophenyl)methyl]imidazol-4-yl]methyl]piperazine-1-carboxylate	74504: Inhibition of [1-3H]-GGPP incorporation into biotinylated K4B-Ras peptide by geranylgeranyl transferase in the presence of 5 mM ATP	ic50	0.0002	uM

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
bisphenol A	affects expression, increases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Ozone	increases oxidation, increases abundance, affects expression, affects cotreatment	2
Cyclosporine	increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
cobaltous chloride	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
Sch 59228	decreases activity	1
K 7174	increases expression	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fluvastatin	affects cotreatment, increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Asbestos	affects expression	1
Benzo(a)pyrene	affects methylation	1

ChEMBL screening assays

513 unique, capped per target: 438 binding, 75 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1026658	Binding	Inhibition of human recombinant FPTase by Ras farnesyl-protein-transferase assay	Barceloneic acid A, a new farnesyl-protein transferase inhibitor from a Phoma species. — *J Nat Prod*
CHEMBL655474	Functional	In vitro inhibition of Ras processing by COS cells at 20 uM	Inhibitors of farnesyl protein transferase. Synthesis and biological activity of amide and cyanoguanidine derivatives containing a 5,11-dihydro[1]benzthiepin, benzoxepin, and benzazepin [4,3-b]pyridine ring system. — *Bioorg Med Chem Lett*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

30 trials:

NCT	Phase	Status	Title
NCT06231459	Phase 4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	Phase 3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	Phase 3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	Phase 3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	Phase 3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	Phase 3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	Phase 3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	Phase 3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	Phase 2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	Phase 2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	Phase 2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	Phase 1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	Phase 1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	UNKNOWN	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab
NCT05825131	Not specified	RECRUITING	Natural History Study of Participants With Sanfilippo Syndrome Type IIIC
NCT07712003	Not specified	NOT_YET_RECRUITING	Natural History to Assess Disease in Patients With MPS IIIC

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FNTA across ~30M SureChEMBL compounds — explore on Sugi Predict.