NPASS Compound

Structure

CID173815 OpenBabel06191715542D 24 26 0 0 1 0 0 0 0 0999 V2000 -2.5246 1.4358 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6558 2.9150 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8545 -1.4353 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4167 4.6003 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7682 3.7054 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3136 5.0468 0.0000 C 0 5 0 0 0 0 0 0 0 0 0 0 0.4837 -1.8027 0.0000 C 0 5 0 0 0 0 0 0 0 0 0 0 1.6745 0.0153 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6703 0.9758 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6649 -0.0097 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8351 -0.4879 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0118 2.9016 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6745 2.8976 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6827 0.9628 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8227 2.4265 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8443 -0.4697 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8419 2.4166 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8298 1.4611 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8475 1.4507 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0004 0.9761 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8174 3.8484 0.0000 C 0 0 0 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 -1.0655 4.4476 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 0.0004 -0.9662 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 1 14 2 0 0 0 0 3 16 1 0 0 0 0 4 21 1 0 0 0 0 5 21 1 0 0 0 0 6 23 3 0 0 0 0 7 24 3 0 0 0 0 8 9 1 0 0 0 0 8 16 1 0 0 0 0 10 11 1 0 0 0 0 10 14 1 0 0 0 0 11 22 1 0 0 0 0 12 15 1 0 0 0 0 12 17 1 0 0 0 0 13 21 1 0 0 0 0 15 2 1 6 0 0 0 15 18 1 0 0 0 0 16 22 1 6 0 0 0 17 13 1 6 0 0 0 17 19 1 0 0 0 0 18 9 1 1 0 0 0 18 20 1 0 0 0 0 19 14 1 1 0 0 0 19 20 1 0 0 0 0 20 22 1 6 0 0 0 21 23 1 0 0 0 0 22 24 1 6 0 0 0 M CHG 4 6 -1 7 -1 23 1 24 1 M END $$$$

Physi-Chem Properties

Molecular Weight:	324.26
Volume:	372.21
LogP:	5.259
LogD:	4.755
LogS:	-5.512
# Rotatable Bonds:	2
TPSA:	8.72
# H-Bond Aceptor:	2
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.434
Synthetic Accessibility Score:	5.667
Fsp3:	0.818
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.814
MDCK Permeability:	8.092869393294677e-05
Pgp-inhibitor:	0.719
Pgp-substrate:	0.124
Human Intestinal Absorption (HIA):	0.063
20% Bioavailability (F20%):	0.242
30% Bioavailability (F30%):	0.934

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.968
Plasma Protein Binding (PPB):	58.48301696777344%
Volume Distribution (VD):	0.982
Pgp-substrate:	31.347496032714844%

ADMET: Metabolism

CYP1A2-inhibitor:	0.022
CYP1A2-substrate:	0.174
CYP2C19-inhibitor:	0.01
CYP2C19-substrate:	0.227
CYP2C9-inhibitor:	0.008
CYP2C9-substrate:	0.076
CYP2D6-inhibitor:	0.517
CYP2D6-substrate:	0.071
CYP3A4-inhibitor:	0.128
CYP3A4-substrate:	0.34

ADMET: Excretion

Clearance (CL):	9.853
Half-life (T1/2):	0.278

ADMET: Toxicity

hERG Blockers:	0.452
Human Hepatotoxicity (H-HT):	0.35
Drug-inuced Liver Injury (DILI):	0.929
AMES Toxicity:	0.083
Rat Oral Acute Toxicity:	0.979
Maximum Recommended Daily Dose:	0.921
Skin Sensitization:	0.925
Carcinogencity:	0.482
Eye Corrosion:	0.983
Eye Irritation:	0.758
Respiratory Toxicity:	0.981

Download Data

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

Natural Product: NPC173815

Natural Product ID:	NPC173815
*Common Name:**	Diisocyanoamphilectene
IUPAC Name:	(1S,3aR,4S,6S,6aS,9aS,9bS)-9a-isocyano-6-(2-isocyano-2-methylpropyl)-1,4-dimethyl-7-methylidene-2,3,3a,4,5,6,6a,8,9,9b-decahydro-1H-phenalene
Synonyms:
Standard InCHIKey:	JZQFIFOTCYCVEG-XQOOQLJESA-N
Standard InCHI:	InChI=1S/C22H32N2/c1-14-10-11-22(24-7)16(3)8-9-18-15(2)12-17(19(14)20(18)22)13-21(4,5)23-6/h15-20H,1,8-13H2,2-5H3/t15-,16-,17-,18+,19-,20-,22-/m0/s1
SMILES:	C=C1CC[C@@]2([C@@H](C)CC[C@@H]3[C@@H](C)C[C@@H](CC(C)(C)[N+]#[C-])[C@H]1[C@@H]23)[N+]#[C-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL522749
PubChem CID:	21778272
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	6
IC50	13
LD50	1
MIC	3
Others	4

Activity Type	# Activity
Cell Line	9
NON-MOLECULAR	6
Organism	6
Others	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	IC50	=	0.7	ug.mL-1	PMID[529991]
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	1.2	ug.mL-1	PMID[529991]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	13.0	ug.mL-1	PMID[529991]
NPT306	Cell Line	PC-3	Homo sapiens	GI50	=	1000.0	nM	PMID[529992]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	42000.0	nM	PMID[529992]
NPT114	Cell Line	LoVo	Homo sapiens	GI50	=	3000.0	nM	PMID[529992]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	GI50	=	6000.0	nM	PMID[529992]
NPT189	Cell Line	Vero	Chlorocebus aethiops	IC50	=	99735.0	nM	PMID[529995]
NPT189	Cell Line	Vero	Chlorocebus aethiops	IC50	=	99740.0	nM	PMID[529996]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	25000.0	nM	PMID[529992]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	50000.0	nM	PMID[529992]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[529993]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	230.0	nM	PMID[529993]
NPT27	Others	Unspecified		IC50	>	10000.0	nM	PMID[529993]
NPT790	Organism	Mycobacterium tuberculosis H37Rv	Mycobacterium tuberculosis H37Rv	MIC	=	2.0	ug.mL-1	PMID[529994]
NPT790	Organism	Mycobacterium tuberculosis H37Rv	Mycobacterium tuberculosis H37Rv	MIC	=	3.2	ug.mL-1	PMID[529995]
NPT757	Organism	Plasmodium falciparum 3D7	Plasmodium falciparum 3D7	IC50	=	1.2	nM	PMID[529995]
NPT27	Others	Unspecified		LD50	>	10.0	uM	PMID[529995]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	230.0	nM	PMID[529995]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[529995]
NPT2	Others	Unspecified		Ratio IC50	=	83112.0	n.a.	PMID[529995]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	3.1	nM	PMID[529996]
NPT757	Organism	Plasmodium falciparum 3D7	Plasmodium falciparum 3D7	IC50	=	1.2	nM	PMID[529996]
NPT790	Organism	Mycobacterium tuberculosis H37Rv	Mycobacterium tuberculosis H37Rv	MIC	=	9800.0	nM	PMID[529996]
NPT2	Others	Unspecified		Ratio IC50	=	32174.0	n.a.	PMID[529996]
NPT2	Others	Unspecified		Ratio IC50	=	83117.0	n.a.	PMID[529996]
NPT2	Others	Unspecified		Selectivity Index	=	10.2	n.a.	PMID[529996]

☑ 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 NPC173815 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	335
0.1-0.2	11916
0.2-0.3	19720
0.3-0.4	8162
0.4-0.5	2272
0.5-0.6	228
0.6-0.7	39
0.7-0.8	17
0.8-0.85	4
0.85-0.9	0
0.9-0.95	1
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9815	High Similarity	NPC324944
0.9444	High Similarity	NPC318036
0.8793	High Similarity	NPC317778
0.8095	Intermediate Similarity	NPC474456
0.8036	Intermediate Similarity	NPC212905
0.8	Intermediate Similarity	NPC28755
0.8	Intermediate Similarity	NPC152211
0.7969	Intermediate Similarity	NPC476135
0.7586	Intermediate Similarity	NPC474416
0.75	Intermediate Similarity	NPC476329
0.7463	Intermediate Similarity	NPC138409
0.7463	Intermediate Similarity	NPC184919
0.7377	Intermediate Similarity	NPC470369
0.7377	Intermediate Similarity	NPC470370
0.7344	Intermediate Similarity	NPC145715
0.7231	Intermediate Similarity	NPC476682
0.7231	Intermediate Similarity	NPC473959
0.7188	Intermediate Similarity	NPC219621
0.7097	Intermediate Similarity	NPC474457
0.7083	Intermediate Similarity	NPC476308
0.7069	Intermediate Similarity	NPC476681
0.6875	Remote Similarity	NPC472827
0.6875	Remote Similarity	NPC474420
0.6875	Remote Similarity	NPC474455
0.6875	Remote Similarity	NPC474454
0.6825	Remote Similarity	NPC474528
0.6825	Remote Similarity	NPC474415
0.6825	Remote Similarity	NPC475696
0.6818	Remote Similarity	NPC474027
0.6818	Remote Similarity	NPC474435
0.6818	Remote Similarity	NPC475755
0.6806	Remote Similarity	NPC476904
0.6769	Remote Similarity	NPC311809
0.6761	Remote Similarity	NPC21773
0.6761	Remote Similarity	NPC265789
0.6727	Remote Similarity	NPC193180
0.6721	Remote Similarity	NPC127944
0.6615	Remote Similarity	NPC475716
0.661	Remote Similarity	NPC22765
0.6579	Remote Similarity	NPC211322
0.6567	Remote Similarity	NPC89921
0.6545	Remote Similarity	NPC103290
0.6522	Remote Similarity	NPC37792
0.6508	Remote Similarity	NPC469770
0.6486	Remote Similarity	NPC125828
0.64	Remote Similarity	NPC7214
0.6364	Remote Similarity	NPC21781
0.6349	Remote Similarity	NPC476683
0.6338	Remote Similarity	NPC476288
0.6333	Remote Similarity	NPC17518
0.6234	Remote Similarity	NPC79704
0.6203	Remote Similarity	NPC329782
0.6167	Remote Similarity	NPC124851
0.614	Remote Similarity	NPC105246
0.614	Remote Similarity	NPC190232
0.6125	Remote Similarity	NPC472312
0.6087	Remote Similarity	NPC474086
0.6076	Remote Similarity	NPC12035
0.6049	Remote Similarity	NPC171639
0.6024	Remote Similarity	NPC157479
0.6024	Remote Similarity	NPC56107
0.6024	Remote Similarity	NPC474458
0.6	Remote Similarity	NPC118329
0.6	Remote Similarity	NPC123194
0.6	Remote Similarity	NPC53276
0.6	Remote Similarity	NPC152039
0.5952	Remote Similarity	NPC43308
0.5938	Remote Similarity	NPC472828
0.5932	Remote Similarity	NPC202189
0.5926	Remote Similarity	NPC283277
0.5926	Remote Similarity	NPC215474
0.5915	Remote Similarity	NPC469970
0.5904	Remote Similarity	NPC152684
0.5904	Remote Similarity	NPC147513
0.589	Remote Similarity	NPC271640
0.5875	Remote Similarity	NPC250632
0.5857	Remote Similarity	NPC472544
0.5833	Remote Similarity	NPC86683
0.5811	Remote Similarity	NPC472831
0.5806	Remote Similarity	NPC106990
0.5802	Remote Similarity	NPC474122
0.5802	Remote Similarity	NPC90150
0.5802	Remote Similarity	NPC257962
0.5789	Remote Similarity	NPC78551
0.5789	Remote Similarity	NPC227632
0.5789	Remote Similarity	NPC62086
0.5763	Remote Similarity	NPC192529
0.5735	Remote Similarity	NPC472830
0.5735	Remote Similarity	NPC469769
0.5735	Remote Similarity	NPC231129
0.5714	Remote Similarity	NPC311769
0.5714	Remote Similarity	NPC24733
0.5714	Remote Similarity	NPC182106
0.5698	Remote Similarity	NPC259252
0.5694	Remote Similarity	NPC27243
0.5694	Remote Similarity	NPC476737
0.5692	Remote Similarity	NPC476679
0.5652	Remote Similarity	NPC82919
0.5647	Remote Similarity	NPC166458
0.5634	Remote Similarity	NPC474596
0.5616	Remote Similarity	NPC107704
0.5616	Remote Similarity	NPC39462
0.5616	Remote Similarity	NPC43300
0.5616	Remote Similarity	NPC168824
0.5616	Remote Similarity	NPC96812
0.5616	Remote Similarity	NPC189917
0.561	Remote Similarity	NPC475724
0.56	Remote Similarity	NPC124384
0.56	Remote Similarity	NPC245223

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 NPC173815 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	261
0.1-0.2	3093
0.2-0.3	4506
0.3-0.4	1100
0.4-0.5	169
0.5-0.6	15
0.6-0.7	6
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
0.6528	Remote Similarity	NPD5365	Phase 2
0.625	Remote Similarity	NPD346	Approved
0.625	Remote Similarity	NPD347	Approved
0.6207	Remote Similarity	NPD871	Approved
0.6207	Remote Similarity	NPD873	Approved
0.614	Remote Similarity	NPD1799	Clinical (unspecified phase)
0.5946	Remote Similarity	NPD6939	Phase 2
0.5946	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