NPASS Compound

Structure

CID318549 OpenBabel06191716142D 29 28 0 0 0 0 0 0 0 0999 V2000 8.0622 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7942 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1962 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 -4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0622 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4641 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9282 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0622 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3301 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1340 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1340 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9282 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1962 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 -3.0000 0.0000 C 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 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 -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 -0.0000 0.0000 P 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 0.0000 0.0000 P 0 0 3 0 0 0 0 0 0 0 0 0 1 17 1 0 0 0 0 2 17 1 0 0 0 0 3 18 1 0 0 0 0 4 19 1 0 0 0 0 5 20 1 0 0 0 0 6 9 1 0 0 0 0 6 10 1 0 0 0 0 7 11 1 0 0 0 0 7 12 1 0 0 0 0 8 13 1 0 0 0 0 8 14 1 0 0 0 0 9 17 2 0 0 0 0 10 18 1 0 0 0 0 11 18 2 0 0 0 0 12 19 1 0 0 0 0 13 19 2 0 0 0 0 14 20 1 0 0 0 0 15 16 1 0 0 0 0 15 20 2 0 0 0 0 16 26 1 0 0 0 0 21 28 1 0 0 0 0 22 28 1 0 0 0 0 23 28 2 0 0 0 0 24 29 1 0 0 0 0 25 29 2 0 0 0 0 26 29 1 0 0 0 0 27 28 1 0 0 0 0 27 29 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	450.19
Volume:	445.116
LogP:	1.838
LogD:	1.122
LogS:	-3.019
# Rotatable Bonds:	14
TPSA:	106.97
# H-Bond Aceptor:	7
# H-Bond Donor:	1
# Rings:	0
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.232
Synthetic Accessibility Score:	4.428
Fsp3:	0.6
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.265
MDCK Permeability:	2.8845828637713566e-05
Pgp-inhibitor:	0.907
Pgp-substrate:	0.009
Human Intestinal Absorption (HIA):	0.897
20% Bioavailability (F20%):	0.873
30% Bioavailability (F30%):	0.852

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.829
Plasma Protein Binding (PPB):	98.5492172241211%
Volume Distribution (VD):	0.547
Pgp-substrate:	0.9779504537582397%

ADMET: Metabolism

CYP1A2-inhibitor:	0.016
CYP1A2-substrate:	0.1
CYP2C19-inhibitor:	0.038
CYP2C19-substrate:	0.05
CYP2C9-inhibitor:	0.127
CYP2C9-substrate:	0.988
CYP2D6-inhibitor:	0.013
CYP2D6-substrate:	0.179
CYP3A4-inhibitor:	0.015
CYP3A4-substrate:	0.033

ADMET: Excretion

Clearance (CL):	1.59
Half-life (T1/2):	0.805

ADMET: Toxicity

hERG Blockers:	0.006
Human Hepatotoxicity (H-HT):	0.121
Drug-inuced Liver Injury (DILI):	0.002
AMES Toxicity:	0.002
Rat Oral Acute Toxicity:	0.003
Maximum Recommended Daily Dose:	0.879
Skin Sensitization:	0.974
Carcinogencity:	0.608
Eye Corrosion:	0.685
Eye Irritation:	0.93
Respiratory Toxicity:	0.75

Download Data

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

Natural Product: NPC318549

Natural Product ID:	NPC318549
*Common Name:**	Phosphoric Acid Di-((2Z,6E,10E)-3,7,11,15-Tetramethyl-Hexadeca-2,6,10,14-Tetraenyl) Ester
IUPAC Name:	phosphono [(2Z,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenyl] hydrogen phosphate
Synonyms:
Standard InCHIKey:	OINNEUNVOZHBOX-KWBDAJKESA-N
Standard InCHI:	InChI=1S/C20H36O7P2/c1-17(2)9-6-10-18(3)11-7-12-19(4)13-8-14-20(5)15-16-26-29(24,25)27-28(21,22)23/h9,11,13,15H,6-8,10,12,14,16H2,1-5H3,(H,24,25)(H2,21,22,23)/b18-11+,19-13+,20-15-
SMILES:	CC(=CCCC(=CCCC(=CCCC(=CCOP(=O)(O)OP(=O)(O)O)C)C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1160061
PubChem CID:	5281909
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001357] Acyclic diterpenoids

*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
IC50	1
Others	2

Activity Type	# Activity
Protein Complex	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1180	Protein Complex	Protein farnesyltransferase	Homo sapiens	Km	=	21.0	nM	PMID[476646]
NPT1180	Protein Complex	Protein farnesyltransferase	Homo sapiens	Krel	=	0.67	n.a.	PMID[476646]
NPT1181	Protein Complex	Geranylgeranyl transferase type I	Homo sapiens	IC50	=	100.0	nM	PMID[476646]

☑ 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 NPC318549 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	13488
0.2-0.3	20073
0.3-0.4	7194
0.4-0.5	1446
0.5-0.6	322
0.6-0.7	26
0.7-0.8	7
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	NPC221379
0.7727	Intermediate Similarity	NPC314888
0.7551	Intermediate Similarity	NPC160628
0.75	Intermediate Similarity	NPC116934
0.7447	Intermediate Similarity	NPC269823
0.7292	Intermediate Similarity	NPC213538
0.7292	Intermediate Similarity	NPC256766
0.72	Intermediate Similarity	NPC140501
0.7119	Intermediate Similarity	NPC149682
0.7021	Intermediate Similarity	NPC255042
0.7021	Intermediate Similarity	NPC182840
0.7021	Intermediate Similarity	NPC29091
0.7021	Intermediate Similarity	NPC103213
0.7	Intermediate Similarity	NPC138935
0.6957	Remote Similarity	NPC315093
0.6939	Remote Similarity	NPC318351
0.6739	Remote Similarity	NPC314319
0.6667	Remote Similarity	NPC474460
0.6545	Remote Similarity	NPC473672
0.6545	Remote Similarity	NPC474495
0.6481	Remote Similarity	NPC267110
0.6415	Remote Similarity	NPC308331
0.6415	Remote Similarity	NPC197467
0.6364	Remote Similarity	NPC182102
0.6364	Remote Similarity	NPC26960
0.6346	Remote Similarity	NPC12907
0.6327	Remote Similarity	NPC15934
0.6316	Remote Similarity	NPC474496
0.6226	Remote Similarity	NPC26600
0.6226	Remote Similarity	NPC47946
0.6167	Remote Similarity	NPC249850
0.6167	Remote Similarity	NPC129150
0.6167	Remote Similarity	NPC294938
0.6167	Remote Similarity	NPC293437
0.6136	Remote Similarity	NPC115959
0.6136	Remote Similarity	NPC123965
0.6111	Remote Similarity	NPC128280
0.6078	Remote Similarity	NPC469713
0.6066	Remote Similarity	NPC223679
0.6066	Remote Similarity	NPC254095
0.6066	Remote Similarity	NPC21946
0.6038	Remote Similarity	NPC6963
0.6038	Remote Similarity	NPC304079
0.6029	Remote Similarity	NPC324638
0.6	Remote Similarity	NPC277382
0.6	Remote Similarity	NPC171978
0.5968	Remote Similarity	NPC82465
0.5965	Remote Similarity	NPC55383
0.5962	Remote Similarity	NPC304151
0.5962	Remote Similarity	NPC206906
0.5926	Remote Similarity	NPC270706
0.5926	Remote Similarity	NPC269074
0.5902	Remote Similarity	NPC268185
0.5902	Remote Similarity	NPC135863
0.5893	Remote Similarity	NPC85079
0.5893	Remote Similarity	NPC248884
0.5893	Remote Similarity	NPC31194
0.5893	Remote Similarity	NPC153538
0.5893	Remote Similarity	NPC135698
0.5882	Remote Similarity	NPC18205
0.5882	Remote Similarity	NPC12319
0.587	Remote Similarity	NPC471327
0.5862	Remote Similarity	NPC35756
0.5833	Remote Similarity	NPC281590
0.5833	Remote Similarity	NPC329686
0.5833	Remote Similarity	NPC58957
0.5818	Remote Similarity	NPC35141
0.5818	Remote Similarity	NPC124183
0.5818	Remote Similarity	NPC180575
0.5806	Remote Similarity	NPC23418
0.5806	Remote Similarity	NPC226848
0.5806	Remote Similarity	NPC181872
0.58	Remote Similarity	NPC180840
0.58	Remote Similarity	NPC40434
0.58	Remote Similarity	NPC34873
0.5789	Remote Similarity	NPC236338
0.5789	Remote Similarity	NPC473913
0.5789	Remote Similarity	NPC72699
0.5789	Remote Similarity	NPC477727
0.5789	Remote Similarity	NPC225974
0.5789	Remote Similarity	NPC249670
0.5789	Remote Similarity	NPC288381
0.5789	Remote Similarity	NPC291437
0.5789	Remote Similarity	NPC328784
0.5789	Remote Similarity	NPC474642
0.5789	Remote Similarity	NPC471281
0.5789	Remote Similarity	NPC199286
0.5789	Remote Similarity	NPC20934
0.5763	Remote Similarity	NPC217188
0.5738	Remote Similarity	NPC96663
0.5714	Remote Similarity	NPC122239
0.5714	Remote Similarity	NPC475931
0.569	Remote Similarity	NPC59408
0.569	Remote Similarity	NPC329608
0.569	Remote Similarity	NPC244038
0.569	Remote Similarity	NPC224148
0.569	Remote Similarity	NPC76198
0.569	Remote Similarity	NPC165447
0.569	Remote Similarity	NPC89824
0.569	Remote Similarity	NPC475477
0.569	Remote Similarity	NPC151782
0.569	Remote Similarity	NPC9273
0.569	Remote Similarity	NPC471959
0.569	Remote Similarity	NPC477723
0.569	Remote Similarity	NPC93639
0.569	Remote Similarity	NPC197272
0.569	Remote Similarity	NPC170776
0.569	Remote Similarity	NPC256656
0.569	Remote Similarity	NPC71053
0.569	Remote Similarity	NPC294278
0.5667	Remote Similarity	NPC189677
0.566	Remote Similarity	NPC51758
0.566	Remote Similarity	NPC209279
0.566	Remote Similarity	NPC180871
0.566	Remote Similarity	NPC68889
0.566	Remote Similarity	NPC67761
0.566	Remote Similarity	NPC88079
0.566	Remote Similarity	NPC194586
0.566	Remote Similarity	NPC108494
0.5652	Remote Similarity	NPC127145
0.5652	Remote Similarity	NPC137620
0.5652	Remote Similarity	NPC474675
0.5652	Remote Similarity	NPC475930
0.5645	Remote Similarity	NPC52012
0.5645	Remote Similarity	NPC283502
0.5645	Remote Similarity	NPC11130
0.5636	Remote Similarity	NPC165651
0.5636	Remote Similarity	NPC210560
0.5636	Remote Similarity	NPC76976
0.5636	Remote Similarity	NPC24824
0.5625	Remote Similarity	NPC158368
0.5625	Remote Similarity	NPC99088
0.5625	Remote Similarity	NPC154908
0.5625	Remote Similarity	NPC252851
0.5625	Remote Similarity	NPC130807
0.5625	Remote Similarity	NPC173592
0.5625	Remote Similarity	NPC250734
0.5625	Remote Similarity	NPC305759
0.5625	Remote Similarity	NPC226872
0.5625	Remote Similarity	NPC79756
0.5614	Remote Similarity	NPC471276
0.5614	Remote Similarity	NPC471275
0.5614	Remote Similarity	NPC471280
0.5614	Remote Similarity	NPC125122
0.56	Remote Similarity	NPC195109
0.56	Remote Similarity	NPC185839

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 NPC318549 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	123
0.1-0.2	5791
0.2-0.3	2817
0.3-0.4	342
0.4-0.5	62
0.5-0.6	11
0.6-0.7	2
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
0.875	High Similarity	NPD2268	Discontinued
0.7609	Intermediate Similarity	NPD1153	Clinical (unspecified phase)
0.72	Intermediate Similarity	NPD4265	Approved
0.629	Remote Similarity	NPD6949	Clinical (unspecified phase)
0.625	Remote Similarity	NPD6927	Phase 3
0.6029	Remote Similarity	NPD3212	Clinical (unspecified phase)
0.6	Remote Similarity	NPD5783	Phase 3
0.5893	Remote Similarity	NPD4220	Pre-registration

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