NPASS Compound

Structure

NPC212905 OpenBabel07101718192D 24 27 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 0.3712 -2.1581 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 1.9836 -2.7909 0.0000 C 0 5 0 0 0 0 0 0 0 0 0 0 -3.5441 -1.0394 0.0000 C 0 5 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 -1.7321 -1.0000 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 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 -0.0000 -1.0000 0.0000 C 0 0 1 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 -0.8660 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 0.7366 -1.2272 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 1.3601 -2.0090 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 -2.9206 -0.2575 0.0000 N 0 3 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 23 3 0 0 0 0 6 24 3 0 0 0 0 7 8 1 0 0 0 0 7 17 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 14 1 0 0 0 0 12 15 1 0 0 0 0 13 1 1 6 0 0 0 13 16 1 0 0 0 0 14 22 1 6 0 0 0 15 11 1 6 0 0 0 15 19 1 0 0 0 0 16 9 1 1 0 0 0 16 20 1 0 0 0 0 17 20 1 0 0 0 0 17 21 1 1 0 0 0 18 19 1 0 0 0 0 18 22 1 6 0 0 0 19 20 1 0 0 0 0 21 23 1 0 0 0 0 22 24 1 0 0 0 0 M CHG 4 5 -1 6 -1 23 1 24 1 M END $$$$

Physi-Chem Properties

Molecular Weight:	324.26
Volume:	366.29
LogP:	5.247
LogD:	5.17
LogS:	-5.158
# Rotatable Bonds:	0
TPSA:	8.72
# H-Bond Aceptor:	2
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.505
Synthetic Accessibility Score:	5.57
Fsp3:	0.909
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.717
MDCK Permeability:	7.266795000759885e-05
Pgp-inhibitor:	0.997
Pgp-substrate:	0.833
Human Intestinal Absorption (HIA):	0.051
20% Bioavailability (F20%):	0.713
30% Bioavailability (F30%):	0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.935
Plasma Protein Binding (PPB):	70.70086669921875%
Volume Distribution (VD):	0.926
Pgp-substrate:	16.356416702270508%

ADMET: Metabolism

CYP1A2-inhibitor:	0.124
CYP1A2-substrate:	0.967
CYP2C19-inhibitor:	0.01
CYP2C19-substrate:	0.514
CYP2C9-inhibitor:	0.009
CYP2C9-substrate:	0.038
CYP2D6-inhibitor:	0.059
CYP2D6-substrate:	0.037
CYP3A4-inhibitor:	0.637
CYP3A4-substrate:	0.303

ADMET: Excretion

Clearance (CL):	12.968
Half-life (T1/2):	0.717

ADMET: Toxicity

hERG Blockers:	0.264
Human Hepatotoxicity (H-HT):	0.594
Drug-inuced Liver Injury (DILI):	0.888
AMES Toxicity:	0.021
Rat Oral Acute Toxicity:	0.973
Maximum Recommended Daily Dose:	0.92
Skin Sensitization:	0.928
Carcinogencity:	0.163
Eye Corrosion:	0.992
Eye Irritation:	0.768
Respiratory Toxicity:	0.986

Download Data

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

Natural Product: NPC212905

Natural Product ID:	NPC212905
*Common Name:**	Diisocyanoadociane
IUPAC Name:	(2R,3R,3aS,5aS,6S,8aR,9S,10aS,10bS,10cS)-3,6-diisocyano-2,3,6,9-tetramethyl-1,2,3a,4,5,5a,7,8,8a,9,10,10a,10b,10c-tetradecahydropyrene
Synonyms:	Diisocyanoadociane
Standard InCHIKey:	XLVAONKBFLGZSE-OXEUSEQRSA-N
Standard InCHI:	InChI=1S/C22H32N2/c1-13-11-15-12-14(2)22(4,24-6)18-8-7-17-20(19(15)18)16(13)9-10-21(17,3)23-5/h13-20H,7-12H2,1-4H3/t13-,14+,15-,16+,17-,18-,19+,20+,21-,22+/m0/s1
SMILES:	C[C@H]1C[C@H]2C[C@@H](C)[C@](C)([C@H]3CC[C@H]4[C@@H]([C@@H]1CC[C@]4(C)[N+]#[C-])[C@H]23)[N+]#[C-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL353048
PubChem CID:	194103
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
EC50	1
IC50	5
Others	4

Activity Type	# Activity
Cell Line	1
Organism	6
Others	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	IC50	=	4.7	ug.mL-1	PMID[471368]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	14.48	nM	PMID[471367]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.0047	ug.mL-1	PMID[471368]
NPT2	Others	Unspecified		Ratio IC50	=	1000.0	n.a.	PMID[471368]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.0043	ug.mL-1	PMID[471368]
NPT2	Others	Unspecified		Ratio IC50	=	1100.0	n.a.	PMID[471368]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	14.48	nM	PMID[471369]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	GI	=	98.3	%	PMID[471370]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	EC50	=	13.0	nM	PMID[471371]
NPT2	Others	Unspecified		Selectivity Index	=	1000.0	n.a.	PMID[471371]

☑ 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 NPC212905 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	1074
0.1-0.2	25249
0.2-0.3	10761
0.3-0.4	4897
0.4-0.5	599
0.5-0.6	76
0.6-0.7	30
0.7-0.8	5
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8276	Intermediate Similarity	NPC475755
0.8276	Intermediate Similarity	NPC474435
0.8276	Intermediate Similarity	NPC474027
0.8214	Intermediate Similarity	NPC324944
0.8036	Intermediate Similarity	NPC173815
0.7966	Intermediate Similarity	NPC89921
0.7857	Intermediate Similarity	NPC318036
0.7619	Intermediate Similarity	NPC476288
0.7333	Intermediate Similarity	NPC317778
0.7167	Intermediate Similarity	NPC21781
0.6719	Remote Similarity	NPC53276
0.6667	Remote Similarity	NPC476135
0.6615	Remote Similarity	NPC469970
0.6567	Remote Similarity	NPC271640
0.6515	Remote Similarity	NPC474456
0.6471	Remote Similarity	NPC138409
0.6471	Remote Similarity	NPC184919
0.6441	Remote Similarity	NPC472828
0.6349	Remote Similarity	NPC152211
0.6349	Remote Similarity	NPC28755
0.6286	Remote Similarity	NPC476329
0.6232	Remote Similarity	NPC245223
0.6232	Remote Similarity	NPC124384
0.6164	Remote Similarity	NPC476308
0.6143	Remote Similarity	NPC473442
0.6143	Remote Similarity	NPC120167
0.6061	Remote Similarity	NPC145715
0.6061	Remote Similarity	NPC477740
0.6032	Remote Similarity	NPC470370
0.6032	Remote Similarity	NPC470369
0.597	Remote Similarity	NPC473959
0.5932	Remote Similarity	NPC472829
0.5909	Remote Similarity	NPC477739
0.5902	Remote Similarity	NPC474416
0.5902	Remote Similarity	NPC475272
0.5846	Remote Similarity	NPC472827
0.5735	Remote Similarity	NPC476682
0.5733	Remote Similarity	NPC25110
0.5676	Remote Similarity	NPC476904
0.5672	Remote Similarity	NPC219621
0.5645	Remote Similarity	NPC127944
0.5616	Remote Similarity	NPC110615
0.5616	Remote Similarity	NPC21773
0.5606	Remote Similarity	NPC474420
0.5606	Remote Similarity	NPC474455
0.5606	Remote Similarity	NPC474454

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 NPC212905 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	569
0.1-0.2	5813
0.2-0.3	2351
0.3-0.4	325
0.4-0.5	75
0.5-0.6	7
0.6-0.7	6
0.7-0.8	4
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
0.6863	Remote Similarity	NPD346	Approved
0.6863	Remote Similarity	NPD347	Approved
0.6792	Remote Similarity	NPD871	Approved
0.6792	Remote Similarity	NPD873	Approved
0.5965	Remote Similarity	NPD872	Approved
0.5965	Remote Similarity	NPD874	Approved
0.5806	Remote Similarity	NPD3727	Discontinued
0.5738	Remote Similarity	NPD3721	Approved
0.5738	Remote Similarity	NPD3722	Approved
0.5667	Remote Similarity	NPD4834	Discontinued
0.566	Remote Similarity	NPD635	Phase 3
0.566	Remote Similarity	NPD636	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