NPASS Compound

Structure

NPC473959 OpenBabel07101719132D 22 23 0 0 1 0 0 0 0 0999 V2000 -3.4641 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 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 -0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -3.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0000 -2.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 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 -0.5000 0.8660 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 2.5981 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 15 1 0 0 0 0 2 15 1 0 0 0 0 5 6 1 0 0 0 0 5 10 2 0 0 0 0 6 11 1 0 0 0 0 7 8 1 0 0 0 0 7 9 1 0 0 0 0 8 15 2 0 0 0 0 9 16 1 0 0 0 0 11 19 1 0 0 0 0 12 13 1 0 0 0 0 12 17 1 0 0 0 0 13 20 1 0 0 0 0 14 21 2 0 0 0 0 14 22 2 0 0 0 0 16 3 1 6 0 0 0 17 16 1 1 0 0 0 17 18 1 0 0 0 0 18 10 1 6 0 0 0 18 19 1 0 0 0 0 19 20 1 1 0 0 0 20 4 1 1 0 0 0 20 21 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	317.22
Volume:	356.323
LogP:	7.912
LogD:	6.185
LogS:	-6.641
# Rotatable Bonds:	5
TPSA:	12.36
# H-Bond Aceptor:	1
# H-Bond Donor:	0
# Rings:	2
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.333
Synthetic Accessibility Score:	4.907
Fsp3:	0.75
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:	-4.551
MDCK Permeability:	1.7360225683660246e-05
Pgp-inhibitor:	0.565
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.006
20% Bioavailability (F20%):	0.029
30% Bioavailability (F30%):	0.024

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.871
Plasma Protein Binding (PPB):	97.18012237548828%
Volume Distribution (VD):	3.627
Pgp-substrate:	2.4450032711029053%

ADMET: Metabolism

CYP1A2-inhibitor:	0.423
CYP1A2-substrate:	0.287
CYP2C19-inhibitor:	0.059
CYP2C19-substrate:	0.918
CYP2C9-inhibitor:	0.211
CYP2C9-substrate:	0.129
CYP2D6-inhibitor:	0.035
CYP2D6-substrate:	0.101
CYP3A4-inhibitor:	0.933
CYP3A4-substrate:	0.412

ADMET: Excretion

Clearance (CL):	10.061
Half-life (T1/2):	0.053

ADMET: Toxicity

hERG Blockers:	0.024
Human Hepatotoxicity (H-HT):	0.168
Drug-inuced Liver Injury (DILI):	0.708
AMES Toxicity:	0.008
Rat Oral Acute Toxicity:	0.163
Maximum Recommended Daily Dose:	0.109
Skin Sensitization:	0.95
Carcinogencity:	0.292
Eye Corrosion:	0.968
Eye Irritation:	0.917
Respiratory Toxicity:	0.733

Download Data

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

Natural Product: NPC473959

Natural Product ID:	NPC473959
*Common Name:**	(1R,4S,4As,8Ar)-4-Isothiocyanato-4-Methyl-1-((R)-6-Methylhept-5-En-2-Yl)-1,2,3,4,4A,5,6,8A-Octahydronaphthalene
IUPAC Name:	(1R,4S,4aS,8aR)-4-isothiocyanato-4-methyl-1-[(2R)-6-methylhept-5-en-2-yl]-2,3,4a,5,6,8a-hexahydro-1H-naphthalene
Synonyms:
Standard InCHIKey:	KZXDVJJOMQYNRC-UEDWAMCQSA-N
Standard InCHI:	InChI=1S/C20H31NS/c1-15(2)8-7-9-16(3)17-12-13-20(4,21-14-22)19-11-6-5-10-18(17)19/h5,8,10,16-19H,6-7,9,11-13H2,1-4H3/t16-,17-,18-,19+,20+/m1/s1
SMILES:	CC(CCC=C(C)C)C1CCC(C2C1C=CCC2)(C)N=C=S
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL456305
PubChem CID:	44584208
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids

*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	3

Activity Type	# Activity
Cell Line	1
Organism	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	IC50	>	20.0	ug.mL-1	PMID[521902]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	>	10.0	ug.mL-1	PMID[521902]

☑ 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 NPC473959 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	289
0.1-0.2	5813
0.2-0.3	24050
0.3-0.4	10254
0.4-0.5	2048
0.5-0.6	178
0.6-0.7	47
0.7-0.8	9
0.8-0.85	4
0.85-0.9	3
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9831	High Similarity	NPC145715
0.8923	High Similarity	NPC184919
0.8852	High Similarity	NPC311809
0.8667	High Similarity	NPC470370
0.8667	High Similarity	NPC470369
0.8387	Intermediate Similarity	NPC152211
0.8387	Intermediate Similarity	NPC28755
0.8254	Intermediate Similarity	NPC317778
0.8182	Intermediate Similarity	NPC37792
0.8088	Intermediate Similarity	NPC138409
0.7733	Intermediate Similarity	NPC250632
0.7619	Intermediate Similarity	NPC318036
0.7606	Intermediate Similarity	NPC476329
0.7432	Intermediate Similarity	NPC476308
0.7403	Intermediate Similarity	NPC475724
0.7385	Intermediate Similarity	NPC324944
0.7313	Intermediate Similarity	NPC219621
0.7231	Intermediate Similarity	NPC173815
0.7143	Intermediate Similarity	NPC474456
0.7042	Intermediate Similarity	NPC476135
0.6951	Remote Similarity	NPC474458
0.6857	Remote Similarity	NPC476682
0.6774	Remote Similarity	NPC17518
0.6765	Remote Similarity	NPC472827
0.6719	Remote Similarity	NPC473728
0.6716	Remote Similarity	NPC474528
0.6716	Remote Similarity	NPC474415
0.6716	Remote Similarity	NPC475696
0.6711	Remote Similarity	NPC476904
0.6667	Remote Similarity	NPC202189
0.6667	Remote Similarity	NPC21773
0.6623	Remote Similarity	NPC125828
0.6613	Remote Similarity	NPC124851
0.6582	Remote Similarity	NPC79704
0.6557	Remote Similarity	NPC86683
0.6522	Remote Similarity	NPC474454
0.6522	Remote Similarity	NPC475716
0.6522	Remote Similarity	NPC474420
0.6522	Remote Similarity	NPC474455
0.6508	Remote Similarity	NPC22765
0.6471	Remote Similarity	NPC474457
0.6447	Remote Similarity	NPC265789
0.64	Remote Similarity	NPC472831
0.6329	Remote Similarity	NPC7214
0.6265	Remote Similarity	NPC283277
0.625	Remote Similarity	NPC475755
0.625	Remote Similarity	NPC106990
0.625	Remote Similarity	NPC474086
0.625	Remote Similarity	NPC472544
0.623	Remote Similarity	NPC192529
0.6176	Remote Similarity	NPC469770
0.6154	Remote Similarity	NPC472829
0.6145	Remote Similarity	NPC329782
0.6143	Remote Similarity	NPC469769
0.6119	Remote Similarity	NPC476679
0.6119	Remote Similarity	NPC475272
0.6104	Remote Similarity	NPC472543
0.6098	Remote Similarity	NPC211322
0.6071	Remote Similarity	NPC472312
0.6071	Remote Similarity	NPC471868
0.6066	Remote Similarity	NPC177470
0.6066	Remote Similarity	NPC105246
0.6066	Remote Similarity	NPC190232
0.6047	Remote Similarity	NPC24733
0.6032	Remote Similarity	NPC241784
0.6032	Remote Similarity	NPC13991
0.6032	Remote Similarity	NPC296337
0.6032	Remote Similarity	NPC114239
0.6024	Remote Similarity	NPC12035
0.6	Remote Similarity	NPC171639
0.597	Remote Similarity	NPC212905
0.5952	Remote Similarity	NPC474122
0.5952	Remote Similarity	NPC118329
0.5952	Remote Similarity	NPC152039
0.5942	Remote Similarity	NPC123194
0.5932	Remote Similarity	NPC139717
0.5932	Remote Similarity	NPC229262
0.5932	Remote Similarity	NPC297643
0.5915	Remote Similarity	NPC231129
0.5915	Remote Similarity	NPC472830
0.5909	Remote Similarity	NPC476681
0.5902	Remote Similarity	NPC144023
0.589	Remote Similarity	NPC469728
0.5882	Remote Similarity	NPC474416
0.5882	Remote Similarity	NPC215474
0.5873	Remote Similarity	NPC248411
0.5862	Remote Similarity	NPC152684
0.5833	Remote Similarity	NPC82919
0.5806	Remote Similarity	NPC193180
0.5797	Remote Similarity	NPC476683
0.5795	Remote Similarity	NPC166458
0.5763	Remote Similarity	NPC76145
0.5763	Remote Similarity	NPC34764
0.5763	Remote Similarity	NPC190810
0.5758	Remote Similarity	NPC17810
0.5738	Remote Similarity	NPC183670
0.5733	Remote Similarity	NPC469662
0.5733	Remote Similarity	NPC476559
0.5714	Remote Similarity	NPC470893
0.5698	Remote Similarity	NPC224072
0.5694	Remote Similarity	NPC60772
0.5672	Remote Similarity	NPC200129
0.5645	Remote Similarity	NPC103290
0.5632	Remote Similarity	NPC21667
0.5618	Remote Similarity	NPC157479
0.5616	Remote Similarity	NPC276764
0.5616	Remote Similarity	NPC472304
0.5604	Remote Similarity	NPC249312
0.56	Remote Similarity	NPC202118
0.56	Remote Similarity	NPC89921
0.56	Remote Similarity	NPC174956
0.56	Remote Similarity	NPC197238
0.56	Remote Similarity	NPC474596
0.56	Remote Similarity	NPC474027
0.56	Remote Similarity	NPC474435

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 NPC473959 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	205
0.1-0.2	1813
0.2-0.3	5191
0.3-0.4	1648
0.4-0.5	282
0.5-0.6	10
0.6-0.7	1
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
0.6104	Remote Similarity	NPD6939	Phase 2
0.6104	Remote Similarity	NPD6938	Clinical (unspecified phase)
0.6066	Remote Similarity	NPD1799	Clinical (unspecified phase)
0.6026	Remote Similarity	NPD5365	Phase 2
0.5763	Remote Similarity	NPD319	Phase 1
0.5758	Remote Similarity	NPD8262	Approved
0.5699	Remote Similarity	NPD5771	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