NPASS Compound

Structure

CID318036 OpenBabel06191716142D 22 24 0 0 1 0 0 0 0 0999 V2000 -2.4990 3.3542 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8385 3.3536 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5169 0.4584 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6513 1.9333 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8523 -2.4043 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4199 -1.2980 0.0000 C 0 5 0 0 0 0 0 0 0 0 0 0 -1.6596 -0.9829 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8323 -1.4597 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6658 -0.0002 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6699 -0.9579 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6692 1.9159 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0114 1.9199 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6689 2.8746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6774 -0.0132 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8207 1.4462 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8391 1.4363 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8278 0.4836 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0004 -0.9732 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8447 0.4733 0.0000 C 0 0 1 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 0.8422 -1.4415 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6799 -1.9076 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 1 13 2 0 0 0 0 2 13 1 0 0 0 0 3 14 2 0 0 0 0 5 21 1 0 0 0 0 6 22 3 0 0 0 0 7 8 1 0 0 0 0 7 14 1 0 0 0 0 8 18 1 0 0 0 0 9 10 1 0 0 0 0 10 21 1 0 0 0 0 11 13 1 0 0 0 0 12 15 1 0 0 0 0 12 16 1 0 0 0 0 15 4 1 6 0 0 0 15 17 1 0 0 0 0 16 11 1 6 0 0 0 16 19 1 0 0 0 0 17 9 1 1 0 0 0 17 20 1 0 0 0 0 18 20 1 0 0 0 0 18 21 1 6 0 0 0 19 14 1 1 0 0 0 19 20 1 0 0 0 0 21 22 1 0 0 0 0 M CHG 2 6 -1 22 1 M END $$$$

Physi-Chem Properties

Molecular Weight:	297.25
Volume:	346.554
LogP:	6.033
LogD:	4.973
LogS:	-5.773
# Rotatable Bonds:	2
TPSA:	4.36
# H-Bond Aceptor:	1
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	1

MedChem Properties

QED Drug-Likeness Score:	0.442
Synthetic Accessibility Score:	5.205
Fsp3:	0.762
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.673
MDCK Permeability:	3.942228067899123e-05
Pgp-inhibitor:	0.003
Pgp-substrate:	0.004
Human Intestinal Absorption (HIA):	0.006
20% Bioavailability (F20%):	0.449
30% Bioavailability (F30%):	0.118

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.902
Plasma Protein Binding (PPB):	71.95848083496094%
Volume Distribution (VD):	1.298
Pgp-substrate:	20.591169357299805%

ADMET: Metabolism

CYP1A2-inhibitor:	0.136
CYP1A2-substrate:	0.73
CYP2C19-inhibitor:	0.019
CYP2C19-substrate:	0.719
CYP2C9-inhibitor:	0.023
CYP2C9-substrate:	0.077
CYP2D6-inhibitor:	0.026
CYP2D6-substrate:	0.128
CYP3A4-inhibitor:	0.646
CYP3A4-substrate:	0.313

ADMET: Excretion

Clearance (CL):	12.669
Half-life (T1/2):	0.229

ADMET: Toxicity

hERG Blockers:	0.117
Human Hepatotoxicity (H-HT):	0.353
Drug-inuced Liver Injury (DILI):	0.87
AMES Toxicity:	0.058
Rat Oral Acute Toxicity:	0.712
Maximum Recommended Daily Dose:	0.888
Skin Sensitization:	0.719
Carcinogencity:	0.735
Eye Corrosion:	0.927
Eye Irritation:	0.486
Respiratory Toxicity:	0.896

Download Data

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

Natural Product: NPC318036

Natural Product ID:	NPC318036
*Common Name:**	(1S,3Ar,3A1S,4S,6S,6As,9Ar)-1-Isocyano-1,4-Dimethyl-6-(2-Methylallyl)-7-Methylenedodecahydro-1H-Phenalene
IUPAC Name:	(1S,3S,3aR,6S,6aR,9aS,9bS)-6-isocyano-3,6-dimethyl-9-methylidene-1-(2-methylprop-2-enyl)-2,3,3a,4,5,6a,7,8,9a,9b-decahydro-1H-phenalene
Synonyms:	7-Isocyano-11(20)-15(16)-amphilectadiene
Standard InCHIKey:	IHQUZDWCMMAOFI-YMJVXHRNSA-N
Standard InCHI:	InChI=1S/C21H31N/c1-13(2)11-16-12-15(4)17-9-10-21(5,22-6)18-8-7-14(3)19(16)20(17)18/h15-20H,1,3,7-12H2,2,4-5H3/t15-,16+,17+,18+,19-,20+,21-/m0/s1
SMILES:	[C-]#[N+][C@@]1(C)CC[C@H]2[C@@H]3[C@H]1CCC(=C)[C@H]3[C@@H](C[C@@H]2C)CC(=C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1911851
PubChem CID:	21778273
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
NPO30154	Pseudaxinella flava	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[21985105]

☑ 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
GI50	1
IC50	3

Activity Type	# Activity
Cell Line	1
NON-MOLECULAR	2
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT306	Cell Line	PC-3	Homo sapiens	GI50	=	7000.0	nM	PMID[503979]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[503980]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	1720.0	nM	PMID[503980]
NPT27	Others	Unspecified		IC50	>	10000.0	nM	PMID[503980]

☑ 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 NPC318036 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	340
0.1-0.2	12117
0.2-0.3	19598
0.3-0.4	8086
0.4-0.5	2273
0.5-0.6	220
0.6-0.7	34
0.7-0.8	23
0.8-0.85	2
0.85-0.9	0
0.9-0.95	1
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.963	High Similarity	NPC324944
0.9444	High Similarity	NPC173815
0.9286	High Similarity	NPC317778
0.8136	Intermediate Similarity	NPC152211
0.8136	Intermediate Similarity	NPC28755
0.8095	Intermediate Similarity	NPC476135
0.7857	Intermediate Similarity	NPC212905
0.7846	Intermediate Similarity	NPC138409
0.7846	Intermediate Similarity	NPC184919
0.7797	Intermediate Similarity	NPC470370
0.7797	Intermediate Similarity	NPC470369
0.7742	Intermediate Similarity	NPC145715
0.7719	Intermediate Similarity	NPC474416
0.7656	Intermediate Similarity	NPC474456
0.7619	Intermediate Similarity	NPC473959
0.7612	Intermediate Similarity	NPC476329
0.7344	Intermediate Similarity	NPC476682
0.7302	Intermediate Similarity	NPC219621
0.7213	Intermediate Similarity	NPC474457
0.7193	Intermediate Similarity	NPC476681
0.7183	Intermediate Similarity	NPC476308
0.6984	Remote Similarity	NPC474454
0.6984	Remote Similarity	NPC474420
0.6984	Remote Similarity	NPC474455
0.6984	Remote Similarity	NPC472827
0.6935	Remote Similarity	NPC474528
0.6935	Remote Similarity	NPC474415
0.6935	Remote Similarity	NPC475696
0.6875	Remote Similarity	NPC311809
0.6852	Remote Similarity	NPC193180
0.6719	Remote Similarity	NPC475716
0.6667	Remote Similarity	NPC103290
0.6667	Remote Similarity	NPC475755
0.6667	Remote Similarity	NPC476904
0.6667	Remote Similarity	NPC474027
0.6667	Remote Similarity	NPC474435
0.662	Remote Similarity	NPC21773
0.6618	Remote Similarity	NPC37792
0.6557	Remote Similarity	NPC127944
0.6452	Remote Similarity	NPC476683
0.6447	Remote Similarity	NPC211322
0.6441	Remote Similarity	NPC22765
0.6418	Remote Similarity	NPC89921
0.6389	Remote Similarity	NPC265789
0.6349	Remote Similarity	NPC469770
0.6316	Remote Similarity	NPC79704
0.6296	Remote Similarity	NPC474458
0.6267	Remote Similarity	NPC7214
0.625	Remote Similarity	NPC105246
0.625	Remote Similarity	NPC190232
0.6212	Remote Similarity	NPC21781
0.6197	Remote Similarity	NPC476288
0.6176	Remote Similarity	NPC474086
0.6167	Remote Similarity	NPC17518
0.6154	Remote Similarity	NPC250632
0.6133	Remote Similarity	NPC125828
0.6076	Remote Similarity	NPC329782
0.6034	Remote Similarity	NPC202189
0.6032	Remote Similarity	NPC472828
0.6	Remote Similarity	NPC124851
0.6	Remote Similarity	NPC472312
0.5949	Remote Similarity	NPC12035
0.5932	Remote Similarity	NPC86683
0.5926	Remote Similarity	NPC171639
0.5904	Remote Similarity	NPC157479
0.5902	Remote Similarity	NPC106990
0.5893	Remote Similarity	NPC78551
0.5893	Remote Similarity	NPC227632
0.5893	Remote Similarity	NPC62086
0.589	Remote Similarity	NPC472831
0.5875	Remote Similarity	NPC118329
0.5875	Remote Similarity	NPC475724
0.5875	Remote Similarity	NPC152039
0.5862	Remote Similarity	NPC192529
0.5857	Remote Similarity	NPC53276
0.5846	Remote Similarity	NPC123194
0.5833	Remote Similarity	NPC43308
0.5821	Remote Similarity	NPC472830
0.5802	Remote Similarity	NPC283277
0.5802	Remote Similarity	NPC215474
0.5783	Remote Similarity	NPC182106
0.5783	Remote Similarity	NPC152684
0.5783	Remote Similarity	NPC147513
0.5783	Remote Similarity	NPC311769
0.5781	Remote Similarity	NPC476679
0.5775	Remote Similarity	NPC469970
0.5765	Remote Similarity	NPC259252
0.5753	Remote Similarity	NPC271640
0.5714	Remote Similarity	NPC56107
0.5714	Remote Similarity	NPC474596
0.5714	Remote Similarity	NPC477740
0.5679	Remote Similarity	NPC257962
0.5679	Remote Similarity	NPC90150
0.5625	Remote Similarity	NPC473728

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 NPC318036 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	281
0.1-0.2	3265
0.2-0.3	4387
0.3-0.4	1031
0.4-0.5	166
0.5-0.6	15
0.6-0.7	5
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
0.6389	Remote Similarity	NPD5365	Phase 2
0.6364	Remote Similarity	NPD347	Approved
0.6364	Remote Similarity	NPD346	Approved
0.6316	Remote Similarity	NPD873	Approved
0.6316	Remote Similarity	NPD871	Approved
0.625	Remote Similarity	NPD1799	Clinical (unspecified phase)
0.5811	Remote Similarity	NPD6939	Phase 2
0.5811	Remote Similarity	NPD6938	Clinical (unspecified phase)

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