Lonafarnib

Details

• Internal ID: da4d9727-8b28-4b6c-b94c-9fa8b021f581
• Taxonomy: Organoheterocyclic compounds > Benzocycloheptapyridines
• IUPAC Name: 4-[2-[4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl]-2-oxoethyl]piperidine-1-carboxamide
• InChI: InChI=1S/C27H31Br2ClN4O2/c28-20-12-19-2-1-18-13-21(30)14-22(29)24(18)25(26(19)32-15-20)17-5-9-33(10-6-17)23(35)11-16-3-7-34(8-4-16)27(31)36/h12-17,25H,1-11H2,(H2,31,36)/t25-/m1/s1
• InChI Key: DHMTURDWPRKSOA-RUZDIDTESA-N
• Popularity: 823 references in papers

Physical and Chemical Properties

• Molecular Formula: C₂₇H₃₁Br₂ClN₄O₂
• Molecular Weight: 638.80 g/mol
• Exact Mass: 638.04818 g/mol
• Topological Polar Surface Area (TPSA): 79.50 Ų
• XlogP: 4.80
• Atomic LogP (AlogP): 5.91
• H-Bond Acceptor: 3
• H-Bond Donor: 1
• Rotatable Bonds: 3

Synonyms

There are no found synonyms.

2D Structure

ADMET Properties (via admetSAR 2)

Target	Value	Probability (raw)	Probability (%)
Human Intestinal Absorption	+	0.9915	99.15%
Caco-2	-	0.8277	82.77%
Blood Brain Barrier	+	0.9250	92.50%
Human oral bioavailability	-	0.5571	55.71%
Subcellular localzation	Mitochondria	0.6641	66.41%
OATP2B1 inhibitior	-	1.0000	100.00%
OATP1B1 inhibitior	+	0.8923	89.23%
OATP1B3 inhibitior	+	0.9441	94.41%
MATE1 inhibitior	-	0.7623	76.23%
OCT2 inhibitior	+	0.7000	70.00%
BSEP inhibitior	+	0.9499	94.99%
P-glycoprotein inhibitior	+	0.8159	81.59%
P-glycoprotein substrate	-	0.5167	51.67%
CYP3A4 substrate	+	0.6744	67.44%
CYP2C9 substrate	-	0.5881	58.81%
CYP2D6 substrate	-	0.8035	80.35%
CYP3A4 inhibition	+	0.5372	53.72%
CYP2C9 inhibition	-	0.6924	69.24%
CYP2C19 inhibition	+	0.5078	50.78%
CYP2D6 inhibition	-	0.8235	82.35%
CYP1A2 inhibition	-	0.6897	68.97%
CYP2C8 inhibition	+	0.7451	74.51%
CYP inhibitory promiscuity	+	0.7760	77.60%
UGT catelyzed	-	0.0000	0.00%
Carcinogenicity (binary)	-	0.7600	76.00%
Carcinogenicity (trinary)	Non-required	0.6429	64.29%
Eye corrosion	-	0.9900	99.00%
Eye irritation	-	0.9571	95.71%
Skin irritation	-	0.7596	75.96%
Skin corrosion	-	0.9363	93.63%
Ames mutagenesis	-	0.5200	52.00%
Human Ether-a-go-go-Related Gene inhibition	+	0.8460	84.60%
Micronuclear	+	0.7300	73.00%
Hepatotoxicity	+	0.5417	54.17%
skin sensitisation	-	0.8605	86.05%
Respiratory toxicity	+	0.8444	84.44%
Reproductive toxicity	+	0.9111	91.11%
Mitochondrial toxicity	+	0.8875	88.75%
Nephrotoxicity	-	0.9217	92.17%
Acute Oral Toxicity (c)	III	0.4982	49.82%
Estrogen receptor binding	+	0.7214	72.14%
Androgen receptor binding	+	0.7438	74.38%
Thyroid receptor binding	+	0.5411	54.11%
Glucocorticoid receptor binding	+	0.6584	65.84%
Aromatase binding	+	0.6159	61.59%
PPAR gamma	+	0.6568	65.68%
Honey bee toxicity	-	0.8697	86.97%
Biodegradation	-	0.8250	82.50%
Crustacea aquatic toxicity	+	0.5500	55.00%
Fish aquatic toxicity	+	0.6633	66.33%

Targets

Proven Targets:

CHEMBL ID	UniProt ID	Name	Min activity	Assay type	Source
CHEMBL4302	P08183	P-glycoprotein 1	2700 nM	IC50	PMID: 18077425
CHEMBL2094108	P49354	Protein farnesyltransferase	378 nM; 1.9 nM	IC50; IC50	via Super-PRED; via Super-PRED
CHEMBL2167	P01112	Transforming protein p21/H-Ras-1	70 nM	IC50	PMID: 19284751

Predicted Targets (via Super-PRED):

CHEMBL ID	UniProt ID	Name	Probability	Model accuracy
CHEMBL3251	P19838	Nuclear factor NF-kappa-B p105 subunit	98.20%	96.09%
CHEMBL335	P18031	Protein-tyrosine phosphatase 1B	97.59%	95.17%
CHEMBL4040	P28482	MAP kinase ERK2	96.06%	83.82%
CHEMBL2047	Q96RI1	Bile acid receptor FXR	95.80%	96.10%
CHEMBL4203	Q9HAZ1	Dual specificity protein kinase CLK4	95.70%	94.45%
CHEMBL2243	O00519	Anandamide amidohydrolase	94.71%	97.53%
CHEMBL3691	Q13822	Autotaxin	94.32%	96.39%
CHEMBL5608	Q16288	NT-3 growth factor receptor	93.68%	95.89%
CHEMBL4685	P14902	Indoleamine 2,3-dioxygenase	93.55%	96.38%
CHEMBL5845	P23415	Glycine receptor subunit alpha-1	92.75%	90.71%
CHEMBL5339	Q5NUL3	G-protein coupled receptor 120	91.31%	95.78%
CHEMBL2781	P19634	Sodium/hydrogen exchanger 1	90.76%	90.24%
CHEMBL241	Q14432	Phosphodiesterase 3A	89.82%	92.94%
CHEMBL5203	P33316	dUTP pyrophosphatase	89.41%	99.18%
CHEMBL1907603	Q05586	Glutamate NMDA receptor; GRIN1/GRIN2B	89.12%	95.89%
CHEMBL1293249	Q13887	Kruppel-like factor 5	89.04%	86.33%
CHEMBL3807	P17706	T-cell protein-tyrosine phosphatase	88.61%	93.00%
CHEMBL3108638	O15164	Transcription intermediary factor 1-alpha	88.39%	95.56%
CHEMBL4005	P42336	PI3-kinase p110-alpha subunit	87.99%	97.47%
CHEMBL2635	P51452	Dual specificity protein phosphatase 3	87.22%	94.00%
CHEMBL3384	Q16512	Protein kinase N1	87.07%	80.71%
CHEMBL5619	P27695	DNA-(apurinic or apyrimidinic site) lyase	87.04%	91.11%
CHEMBL1795139	Q8IU80	Transmembrane protease serine 6	86.89%	98.33%
CHEMBL2730	P21980	Protein-glutamine gamma-glutamyltransferase	84.95%	92.38%
CHEMBL217	P14416	Dopamine D2 receptor	83.81%	95.62%
CHEMBL4462	Q8IXJ6	NAD-dependent deacetylase sirtuin 2	83.25%	90.24%
CHEMBL1907600	Q00535	Cyclin-dependent kinase 5/CDK5 activator 1	83.13%	93.03%
CHEMBL3137262	O60341	LSD1/CoREST complex	82.64%	97.09%
CHEMBL4208	P20618	Proteasome component C5	82.64%	90.00%
CHEMBL5994	O00574	C-X-C chemokine receptor type 6	82.17%	90.00%
CHEMBL5852	Q96P65	Pyroglutamylated RFamide peptide receptor	80.97%	85.00%
CHEMBL5028	O14672	ADAM10	80.75%	97.50%
CHEMBL3474	P14555	Phospholipase A2 group IIA	80.57%	94.05%
CHEMBL2335	P42785	Lysosomal Pro-X carboxypeptidase	80.35%	100.00%

Plants that contains it

• Dichrostachys cinerea

Cross-Links

• PubChem: 148195
• NPASS: NPC471617
• ChEMBL: CHEMBL298734
• LOTUS: LTS0143948
• wikiData: Q3258910