NPASS Compound

Structure

NPC474027 OpenBabel07101718282D 25 28 0 0 1 0 0 0 0 0999 V2000 -1.7321 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1055 -1.7930 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2859 -0.6733 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3712 2.1581 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4311 0.0243 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3735 0.7930 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6026 -1.7272 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9206 0.2575 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9947 2.9399 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2395 -1.2930 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7321 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2971 -0.5243 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7366 1.2272 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5441 1.0394 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.3601 2.0090 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.6294 3.8708 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2 14 1 0 0 0 0 3 21 1 0 0 0 0 4 22 1 0 0 0 0 5 6 1 0 0 0 0 5 17 1 0 0 0 0 6 18 1 0 0 0 0 7 8 1 0 0 0 0 8 22 1 0 0 0 0 9 13 1 0 0 0 0 10 14 1 0 0 0 0 10 15 1 0 0 0 0 11 21 1 0 0 0 0 11 23 3 0 0 0 0 12 24 2 0 0 0 0 12 25 2 0 0 0 0 13 1 1 6 0 0 0 13 16 1 0 0 0 0 14 21 1 6 0 0 0 15 9 1 6 0 0 0 15 19 1 0 0 0 0 16 7 1 1 0 0 0 16 20 1 0 0 0 0 17 19 1 0 0 0 0 17 21 1 6 0 0 0 18 20 1 0 0 0 0 18 22 1 1 0 0 0 19 20 1 0 0 0 0 22 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	340.25
Volume:	375.08
LogP:	5.383
LogD:	5.47
LogS:	-5.719
# Rotatable Bonds:	1
TPSA:	53.22
# H-Bond Aceptor:	3
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.499
Synthetic Accessibility Score:	5.476
Fsp3:	0.909
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.808
MDCK Permeability:	7.439110049745068e-05
Pgp-inhibitor:	0.996
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.911
30% Bioavailability (F30%):	0.247

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.968
Plasma Protein Binding (PPB):	44.10529708862305%
Volume Distribution (VD):	1.633
Pgp-substrate:	32.46296310424805%

ADMET: Metabolism

CYP1A2-inhibitor:	0.372
CYP1A2-substrate:	0.917
CYP2C19-inhibitor:	0.022
CYP2C19-substrate:	0.87
CYP2C9-inhibitor:	0.057
CYP2C9-substrate:	0.056
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.089
CYP3A4-inhibitor:	0.747
CYP3A4-substrate:	0.503

ADMET: Excretion

Clearance (CL):	2.481
Half-life (T1/2):	0.475

ADMET: Toxicity

hERG Blockers:	0.184
Human Hepatotoxicity (H-HT):	0.312
Drug-inuced Liver Injury (DILI):	0.892
AMES Toxicity:	0.023
Rat Oral Acute Toxicity:	0.957
Maximum Recommended Daily Dose:	0.404
Skin Sensitization:	0.967
Carcinogencity:	0.42
Eye Corrosion:	0.997
Eye Irritation:	0.92
Respiratory Toxicity:	0.983

Download Data

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

Natural Product: NPC474027

Natural Product ID:	NPC474027
*Common Name:**	(1R,2R,3As,3A1S,3A2S,5S,5Ar,8S,8As,10As)-8-Isocyanato-1,2,5,8-Tetramethylhexadecahydropyrene-1-Carbonitrile
IUPAC Name:	(1R,2R,3aS,5S,5aR,8S,8aS,10aS,10bS,10cS)-8-isocyanato-1,2,5,8-tetramethyl-2,3,3a,4,5,5a,6,7,8a,9,10,10a,10b,10c-tetradecahydropyrene-1-carbonitrile
Synonyms:
Standard InCHIKey:	PQKVPNQECCMWNB-RMBRTBKZSA-N
Standard InCHI:	InChI=1S/C22H32N2O/c1-13-9-15-10-14(2)21(3,11-23)17-5-6-18-20(19(15)17)16(13)7-8-22(18,4)24-12-25/h13-20H,5-10H2,1-4H3/t13-,14+,15-,16+,17-,18-,19+,20+,21+,22-/m0/s1
SMILES:	CC1CC2CC(C(C3C2C4C1CCC(C4CC3)(C)N=C=O)(C)C#N)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL458701
PubChem CID:	44584211
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003398] Amphilectane, neoamphilectane, cycloamphilectane, and adociane 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
NPO30160	Cymbastela hooperi	Species	Axinellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[19199790]
NPO30160	Cymbastela hooperi	Species	Axinellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO30160	Cymbastela hooperi	Species	Axinellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8759172]

☑ 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	4
Others	2

Activity Type	# Activity
Cell Line	1
Organism	3
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	IC50	=	2.0	ug.mL-1	PMID[501253]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.0749	ug.mL-1	PMID[501253]
NPT2	Others	Unspecified		Ratio IC50	=	27.0	n.a.	PMID[501253]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.0561	ug.mL-1	PMID[501253]
NPT2	Others	Unspecified		Ratio IC50	=	36.0	n.a.	PMID[501253]
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	220.0	nM	PMID[501254]

☑ 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 NPC474027 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	412
0.1-0.2	22053
0.2-0.3	12625
0.3-0.4	6224
0.4-0.5	1234
0.5-0.6	113
0.6-0.7	28
0.7-0.8	3
0.8-0.85	1
0.85-0.9	1
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC474435
0.9016	High Similarity	NPC475755
0.8906	High Similarity	NPC476288
0.8276	Intermediate Similarity	NPC212905
0.7846	Intermediate Similarity	NPC89921
0.7246	Intermediate Similarity	NPC474456
0.7183	Intermediate Similarity	NPC138409
0.697	Remote Similarity	NPC324944
0.6818	Remote Similarity	NPC173815
0.6712	Remote Similarity	NPC245223
0.6712	Remote Similarity	NPC124384
0.6667	Remote Similarity	NPC476135
0.6667	Remote Similarity	NPC318036
0.6623	Remote Similarity	NPC476308
0.6618	Remote Similarity	NPC21781
0.6571	Remote Similarity	NPC477740
0.6486	Remote Similarity	NPC184919
0.6429	Remote Similarity	NPC477739
0.64	Remote Similarity	NPC473442
0.64	Remote Similarity	NPC120167
0.6377	Remote Similarity	NPC28755
0.6377	Remote Similarity	NPC152211
0.6316	Remote Similarity	NPC476329
0.6286	Remote Similarity	NPC317778
0.625	Remote Similarity	NPC476682
0.625	Remote Similarity	NPC53276
0.6212	Remote Similarity	NPC474416
0.6164	Remote Similarity	NPC469970
0.6133	Remote Similarity	NPC271640
0.6	Remote Similarity	NPC472829
0.6	Remote Similarity	NPC25110
0.597	Remote Similarity	NPC472828
0.597	Remote Similarity	NPC475272
0.5915	Remote Similarity	NPC474455
0.5915	Remote Similarity	NPC474454
0.5915	Remote Similarity	NPC474420
0.5897	Remote Similarity	NPC110615
0.5857	Remote Similarity	NPC474457
0.5833	Remote Similarity	NPC257962
0.5797	Remote Similarity	NPC307063
0.5758	Remote Similarity	NPC476681
0.5676	Remote Similarity	NPC145715
0.5647	Remote Similarity	NPC90150
0.5634	Remote Similarity	NPC474415
0.5634	Remote Similarity	NPC475696
0.5634	Remote Similarity	NPC474528
0.56	Remote Similarity	NPC473959

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 NPC474027 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	219
0.1-0.2	5179
0.2-0.3	3209
0.3-0.4	424
0.4-0.5	99
0.5-0.6	13
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.623	Remote Similarity	NPD873	Approved
0.623	Remote Similarity	NPD871	Approved
0.5876	Remote Similarity	NPD7812	Clinical (unspecified phase)
0.5738	Remote Similarity	NPD346	Approved
0.5738	Remote Similarity	NPD347	Approved

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