NPASS Compound

Structure

CID221379 OpenBabel06191716012D 24 23 0 0 0 0 0 0 0 0999 V2000 -8.5000 0.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0000 -0.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5000 -2.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5000 -2.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5000 -1.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5000 -1.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5000 -1.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0000 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5000 -1.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0000 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5000 -1.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -1.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0000 -0.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0000 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 P 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -2.0000 0.0000 P 0 0 3 0 0 0 0 0 0 0 0 0 1 13 1 0 0 0 0 2 13 1 0 0 0 0 3 14 1 0 0 0 0 4 15 1 0 0 0 0 5 7 1 0 0 0 0 5 8 1 0 0 0 0 6 9 1 0 0 0 0 6 10 1 0 0 0 0 7 13 2 0 0 0 0 8 14 1 0 0 0 0 9 14 2 0 0 0 0 10 15 1 0 0 0 0 11 12 1 0 0 0 0 11 15 2 0 0 0 0 12 21 1 0 0 0 0 16 23 1 0 0 0 0 17 23 1 0 0 0 0 18 23 2 0 0 0 0 19 24 1 0 0 0 0 20 24 2 0 0 0 0 21 24 1 0 0 0 0 22 23 1 0 0 0 0 22 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	382.13
Volume:	361.273
LogP:	0.918
LogD:	0.462
LogS:	-2.828
# Rotatable Bonds:	11
TPSA:	106.97
# H-Bond Aceptor:	7
# H-Bond Donor:	1
# Rings:	0
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.397
Synthetic Accessibility Score:	4.553
Fsp3:	0.6
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.394
MDCK Permeability:	3.3501259167678654e-05
Pgp-inhibitor:	0.729
Pgp-substrate:	0.004
Human Intestinal Absorption (HIA):	0.644
20% Bioavailability (F20%):	0.586
30% Bioavailability (F30%):	0.531

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.991
Plasma Protein Binding (PPB):	96.8816909790039%
Volume Distribution (VD):	0.526
Pgp-substrate:	2.3422999382019043%

ADMET: Metabolism

CYP1A2-inhibitor:	0.011
CYP1A2-substrate:	0.09
CYP2C19-inhibitor:	0.036
CYP2C19-substrate:	0.047
CYP2C9-inhibitor:	0.032
CYP2C9-substrate:	0.971
CYP2D6-inhibitor:	0.017
CYP2D6-substrate:	0.118
CYP3A4-inhibitor:	0.009
CYP3A4-substrate:	0.031

ADMET: Excretion

Clearance (CL):	1.649
Half-life (T1/2):	0.821

ADMET: Toxicity

hERG Blockers:	0.003
Human Hepatotoxicity (H-HT):	0.128
Drug-inuced Liver Injury (DILI):	0.006
AMES Toxicity:	0.003
Rat Oral Acute Toxicity:	0.007
Maximum Recommended Daily Dose:	0.911
Skin Sensitization:	0.968
Carcinogencity:	0.629
Eye Corrosion:	0.916
Eye Irritation:	0.97
Respiratory Toxicity:	0.795

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC221379

Natural Product ID:	NPC221379
*Common Name:**	Farnesyl Diphosphate
IUPAC Name:	phosphono [(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl] hydrogen phosphate
Synonyms:	Farnesyl Diphosphate
Standard InCHIKey:	VWFJDQUYCIWHTN-YFVJMOTDSA-N
Standard InCHI:	InChI=1S/C15H28O7P2/c1-13(2)7-5-8-14(3)9-6-10-15(4)11-12-21-24(19,20)22-23(16,17)18/h7,9,11H,5-6,8,10,12H2,1-4H3,(H,19,20)(H2,16,17,18)/b14-9+,15-11+
SMILES:	C/C(=CCOP(=O)(OP(=O)(O)O)O)/CC/C=C(/CCC=C(C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL69330
PubChem CID:	445713
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Kd	3
Ki	1
Others	23

Activity Type	# Activity
Individual Protein	5
Others	13
Protein Complex	8
SINGLE PROTEIN	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1664	Individual Protein	Squalene synthetase	Rattus norvegicus	Km	=	12700.0	nM	PMID[505524]
NPT1664	Individual Protein	Squalene synthetase	Rattus norvegicus	Ki	=	2600.0	nM	PMID[505524]
NPT4221	Individual Protein	Squalene synthetase	Homo sapiens	Km	=	2300.0	nM	PMID[505528]
NPT4221	Individual Protein	Squalene synthetase	Homo sapiens	Vmax	=	4800.0	nmol/min/mg	PMID[505528]
NPT1495	Individual Protein	Geranylgeranyl pyrophosphate synthetase	Homo sapiens	Km	=	710.0	nM	PMID[505529]
NPT5260	Protein Complex	Farnesyltransferase	Saccharomyces cerevisiae S288c	Kd	=	75.0	nM	PMID[505522]
NPT5260	Protein Complex	Farnesyltransferase	Saccharomyces cerevisiae S288c	Km	=	27000.0	nM	PMID[505523]
NPT1180	Protein Complex	Protein farnesyltransferase	Homo sapiens	Km	=	107.0	nM	PMID[505526]
NPT1180	Protein Complex	Protein farnesyltransferase	Homo sapiens	Km	=	40.0	nM	PMID[505527]
NPT1180	Protein Complex	Protein farnesyltransferase	Homo sapiens	K cat	=	0.09	s-1	PMID[505527]
NPT1180	Protein Complex	Protein farnesyltransferase	Homo sapiens	Ratio	=	2000000.0	1/Ms	PMID[505527]
NPT2	Others	Unspecified		Km	=	2800.0	nM	PMID[505528]
NPT2	Others	Unspecified		Vmax	=	0.97	nmol/min/mg	PMID[505528]
NPT2	Others	Unspecified		Km	=	2300.0	nM	PMID[505528]
NPT2	Others	Unspecified		Vmax	=	1.18	nmol/min/mg	PMID[505528]
NPT2	Others	Unspecified		Km	=	3200.0	nM	PMID[505528]
NPT2	Others	Unspecified		Vmax	=	0.75	nmol/min/mg	PMID[505528]
NPT2	Others	Unspecified		Vmax	=	0.98	nmol/min/mg	PMID[505528]
NPT2	Others	Unspecified		Km	=	2500.0	nM	PMID[505528]
NPT2	Others	Unspecified		Km	=	5250.0	nM	PMID[505528]
NPT2	Others	Unspecified		Vmax	=	1428.56	nmol/min/mg	PMID[505528]
NPT26594	SINGLE PROTEIN	Geranylgeranyl pyrophosphate synthase	Saccharomyces cerevisiae S288c	Km	=	3200.0	nM	PMID[505529]
NPT1180	Protein Complex	Protein farnesyltransferase	Homo sapiens	Kd	=	2.0	nM	PMID[505530]
NPT1180	Protein Complex	Protein farnesyltransferase	Homo sapiens	Kcat/Km	=	4.6	10'4/M/s	PMID[505532]
NPT2	Others	Unspecified		Kd	=	35000.0	nM	PMID[505533]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC221379 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	138
0.1-0.2	13960
0.2-0.3	20491
0.3-0.4	6523
0.4-0.5	1261
0.5-0.6	286
0.6-0.7	25
0.7-0.8	10
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9545	High Similarity	NPC318549
0.8095	Intermediate Similarity	NPC314888
0.7333	Intermediate Similarity	NPC29091
0.7333	Intermediate Similarity	NPC182840
0.7333	Intermediate Similarity	NPC255042
0.7333	Intermediate Similarity	NPC103213
0.7273	Intermediate Similarity	NPC315093
0.7234	Intermediate Similarity	NPC318351
0.7143	Intermediate Similarity	NPC160628
0.7083	Intermediate Similarity	NPC116934
0.7045	Intermediate Similarity	NPC314319
0.7021	Intermediate Similarity	NPC269823
0.6875	Remote Similarity	NPC213538
0.6875	Remote Similarity	NPC256766
0.68	Remote Similarity	NPC140501
0.678	Remote Similarity	NPC149682
0.66	Remote Similarity	NPC12907
0.66	Remote Similarity	NPC138935
0.6596	Remote Similarity	NPC15934
0.6471	Remote Similarity	NPC26600
0.6471	Remote Similarity	NPC47946
0.6415	Remote Similarity	NPC267110
0.6346	Remote Similarity	NPC197467
0.6327	Remote Similarity	NPC469713
0.6296	Remote Similarity	NPC474460
0.6275	Remote Similarity	NPC304079
0.6275	Remote Similarity	NPC6963
0.625	Remote Similarity	NPC277382
0.625	Remote Similarity	NPC171978
0.62	Remote Similarity	NPC304151
0.62	Remote Similarity	NPC206906
0.6182	Remote Similarity	NPC473672
0.6182	Remote Similarity	NPC474495
0.6154	Remote Similarity	NPC270706
0.6122	Remote Similarity	NPC12319
0.6122	Remote Similarity	NPC18205
0.6111	Remote Similarity	NPC135698
0.6087	Remote Similarity	NPC58957
0.6071	Remote Similarity	NPC35756
0.6042	Remote Similarity	NPC34873
0.6042	Remote Similarity	NPC40434
0.6038	Remote Similarity	NPC128280
0.6038	Remote Similarity	NPC308331
0.6	Remote Similarity	NPC236338
0.6	Remote Similarity	NPC182102
0.6	Remote Similarity	NPC26960
0.5965	Remote Similarity	NPC474496
0.5893	Remote Similarity	NPC244038
0.5882	Remote Similarity	NPC180871
0.5882	Remote Similarity	NPC67761
0.5882	Remote Similarity	NPC68889
0.5882	Remote Similarity	NPC88079
0.5882	Remote Similarity	NPC108494
0.5882	Remote Similarity	NPC51758
0.5882	Remote Similarity	NPC209279
0.5882	Remote Similarity	NPC194586
0.587	Remote Similarity	NPC250734
0.5862	Remote Similarity	NPC189677
0.5849	Remote Similarity	NPC165651
0.5849	Remote Similarity	NPC269074
0.5849	Remote Similarity	NPC210560
0.5849	Remote Similarity	NPC24824
0.5833	Remote Similarity	NPC129150
0.5833	Remote Similarity	NPC195109
0.5833	Remote Similarity	NPC249850
0.5833	Remote Similarity	NPC185839
0.5833	Remote Similarity	NPC293437
0.5833	Remote Similarity	NPC135863
0.5833	Remote Similarity	NPC294938
0.5818	Remote Similarity	NPC85079
0.5818	Remote Similarity	NPC153538
0.5818	Remote Similarity	NPC31194
0.5818	Remote Similarity	NPC248884
0.58	Remote Similarity	NPC56917
0.5769	Remote Similarity	NPC106819
0.5741	Remote Similarity	NPC124183
0.5741	Remote Similarity	NPC35141
0.5741	Remote Similarity	NPC180575
0.5738	Remote Similarity	NPC254095
0.5738	Remote Similarity	NPC223679
0.5738	Remote Similarity	NPC21946
0.5735	Remote Similarity	NPC324638
0.5714	Remote Similarity	NPC328784
0.5714	Remote Similarity	NPC180840
0.5714	Remote Similarity	NPC288381
0.5714	Remote Similarity	NPC291437
0.5714	Remote Similarity	NPC225974
0.5714	Remote Similarity	NPC72699
0.5714	Remote Similarity	NPC20934
0.569	Remote Similarity	NPC217188
0.5686	Remote Similarity	NPC188596
0.5682	Remote Similarity	NPC138113
0.5682	Remote Similarity	NPC115959
0.5682	Remote Similarity	NPC123965
0.5645	Remote Similarity	NPC82465
0.5625	Remote Similarity	NPC38497
0.5614	Remote Similarity	NPC55383
0.5614	Remote Similarity	NPC93639
0.5614	Remote Similarity	NPC71053
0.5614	Remote Similarity	NPC151782
0.5614	Remote Similarity	NPC59408

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC221379 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	119
0.1-0.2	5812
0.2-0.3	2835
0.3-0.4	319
0.4-0.5	52
0.5-0.6	10
0.6-0.7	1
0.7-0.8	1
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8723	High Similarity	NPD2268	Discontinued
0.7955	Intermediate Similarity	NPD1153	Clinical (unspecified phase)
0.68	Remote Similarity	NPD4265	Approved
0.5968	Remote Similarity	NPD6949	Clinical (unspecified phase)
0.5893	Remote Similarity	NPD6927	Phase 3
0.5818	Remote Similarity	NPD4220	Pre-registration
0.5735	Remote Similarity	NPD3212	Clinical (unspecified phase)
0.56	Remote Similarity	NPD5783	Phase 3

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data