NPASS Compound

Structure

NPC475755 OpenBabel07101718332D 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 S 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:	356.23
Volume:	384.799
LogP:	6.477
LogD:	5.99
LogS:	-5.887
# Rotatable Bonds:	1
TPSA:	36.15
# H-Bond Aceptor:	2
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.443
Synthetic Accessibility Score:	5.52
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:	-4.785
MDCK Permeability:	5.3099334763828665e-05
Pgp-inhibitor:	0.993
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.077
30% Bioavailability (F30%):	0.062

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.947
Plasma Protein Binding (PPB):	64.24214172363281%
Volume Distribution (VD):	1.324
Pgp-substrate:	15.072997093200684%

ADMET: Metabolism

CYP1A2-inhibitor:	0.538
CYP1A2-substrate:	0.817
CYP2C19-inhibitor:	0.021
CYP2C19-substrate:	0.9
CYP2C9-inhibitor:	0.107
CYP2C9-substrate:	0.05
CYP2D6-inhibitor:	0.009
CYP2D6-substrate:	0.081
CYP3A4-inhibitor:	0.933
CYP3A4-substrate:	0.574

ADMET: Excretion

Clearance (CL):	10.192
Half-life (T1/2):	0.327

ADMET: Toxicity

hERG Blockers:	0.04
Human Hepatotoxicity (H-HT):	0.285
Drug-inuced Liver Injury (DILI):	0.941
AMES Toxicity:	0.008
Rat Oral Acute Toxicity:	0.968
Maximum Recommended Daily Dose:	0.888
Skin Sensitization:	0.953
Carcinogencity:	0.255
Eye Corrosion:	0.997
Eye Irritation:	0.891
Respiratory Toxicity:	0.985

Download Data

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

Natural Product: NPC475755

Natural Product ID:	NPC475755
*Common Name:**	(1R,2R,3As,3A1S,3A2S,5S,5Ar,8S,8As,10As)-8-Isothiocyanato-1,2,5,8-Tetramethylhexadecahydropyrene-1-Carbonitrile
IUPAC Name:	(1R,2R,3aS,5S,5aR,8S,8aS,10aS,10bS,10cS)-8-isothiocyanato-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:	QQXBCHYMIFYUTP-RMBRTBKZSA-N
Standard InCHI:	InChI=1S/C22H32N2S/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=S)(C)C#N)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL514250
PubChem CID:	44584210
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	=	1.6	ug.mL-1	PMID[458452]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.0451	ug.mL-1	PMID[458452]
NPT2	Others	Unspecified		Ratio IC50	=	35.0	n.a.	PMID[458452]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.0285	ug.mL-1	PMID[458452]
NPT2	Others	Unspecified		Ratio IC50	=	56.0	n.a.	PMID[458452]
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	126.0	nM	PMID[458453]

☑ 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 NPC475755 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	1244
0.1-0.2	25364
0.2-0.3	10792
0.3-0.4	4757
0.4-0.5	449
0.5-0.6	61
0.6-0.7	22
0.7-0.8	3
0.8-0.85	2
0.85-0.9	0
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9016	High Similarity	NPC474027
0.9016	High Similarity	NPC474435
0.8333	Intermediate Similarity	NPC476288
0.8276	Intermediate Similarity	NPC212905
0.803	Intermediate Similarity	NPC474456
0.7313	Intermediate Similarity	NPC89921
0.7183	Intermediate Similarity	NPC184919
0.7121	Intermediate Similarity	NPC152211
0.7121	Intermediate Similarity	NPC28755
0.697	Remote Similarity	NPC324944
0.6818	Remote Similarity	NPC173815
0.6774	Remote Similarity	NPC472829
0.6719	Remote Similarity	NPC475272
0.6667	Remote Similarity	NPC318036
0.6618	Remote Similarity	NPC21781
0.6486	Remote Similarity	NPC138409
0.6338	Remote Similarity	NPC145715
0.6286	Remote Similarity	NPC317778
0.6267	Remote Similarity	NPC245223
0.6267	Remote Similarity	NPC124384
0.625	Remote Similarity	NPC53276
0.625	Remote Similarity	NPC473959
0.6216	Remote Similarity	NPC476135
0.6212	Remote Similarity	NPC474416
0.6203	Remote Similarity	NPC476308
0.6164	Remote Similarity	NPC469970
0.6133	Remote Similarity	NPC271640
0.6111	Remote Similarity	NPC477740
0.6056	Remote Similarity	NPC311809
0.5972	Remote Similarity	NPC477739
0.597	Remote Similarity	NPC472828
0.5915	Remote Similarity	NPC474455
0.5915	Remote Similarity	NPC474454
0.5915	Remote Similarity	NPC474420
0.5897	Remote Similarity	NPC476329
0.5867	Remote Similarity	NPC37792
0.5857	Remote Similarity	NPC474457
0.5811	Remote Similarity	NPC476682
0.5769	Remote Similarity	NPC473442
0.5769	Remote Similarity	NPC120167
0.5758	Remote Similarity	NPC476681
0.5663	Remote Similarity	NPC79704
0.5634	Remote Similarity	NPC474415
0.5634	Remote Similarity	NPC475696
0.5634	Remote Similarity	NPC474528

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 NPC475755 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	438
0.1-0.2	5862
0.2-0.3	2488
0.3-0.4	286
0.4-0.5	59
0.5-0.6	10
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
0.5738	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