NPASS Compound

Structure

CID324944 OpenBabel06191716182D 24 26 0 0 1 0 0 0 0 0999 V2000 -2.5252 0.4599 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6568 1.9397 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4172 3.6256 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7689 2.7303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8551 -2.4123 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3134 4.0723 0.0000 C 0 5 0 0 0 0 0 0 0 0 0 0 2.5107 -1.4198 0.0000 C 0 5 0 0 0 0 0 0 0 0 0 0 -1.6651 -0.9861 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8351 -1.4645 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6713 -0.0002 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6755 -0.9611 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0114 1.9262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6747 1.9222 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6830 -0.0133 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8234 1.4510 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8419 1.4410 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8305 0.4852 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0004 -0.9764 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8475 0.4748 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 -1.8178 2.8734 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8450 -1.4463 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0656 3.4728 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 1.6855 -1.9139 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 1 14 2 0 0 0 0 3 21 1 0 0 0 0 4 21 1 0 0 0 0 5 22 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 14 1 0 0 0 0 9 18 1 0 0 0 0 10 11 1 0 0 0 0 11 22 1 0 0 0 0 12 15 1 0 0 0 0 12 16 1 0 0 0 0 13 21 1 0 0 0 0 15 2 1 6 0 0 0 15 17 1 0 0 0 0 16 13 1 6 0 0 0 16 19 1 0 0 0 0 17 10 1 1 0 0 0 17 20 1 0 0 0 0 18 20 1 0 0 0 0 18 22 1 6 0 0 0 19 14 1 1 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 6 -1 7 -1 23 1 24 1 M END $$$$

Physi-Chem Properties

Molecular Weight:	324.26
Volume:	372.21
LogP:	5.257
LogD:	4.728
LogS:	-5.713
# 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:	5.508
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:	-4.799
MDCK Permeability:	8.215648995246738e-05
Pgp-inhibitor:	0.692
Pgp-substrate:	0.068
Human Intestinal Absorption (HIA):	0.046
20% Bioavailability (F20%):	0.253
30% Bioavailability (F30%):	0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.946
Plasma Protein Binding (PPB):	72.6397476196289%
Volume Distribution (VD):	0.859
Pgp-substrate:	19.496501922607422%

ADMET: Metabolism

CYP1A2-inhibitor:	0.024
CYP1A2-substrate:	0.576
CYP2C19-inhibitor:	0.008
CYP2C19-substrate:	0.152
CYP2C9-inhibitor:	0.004
CYP2C9-substrate:	0.082
CYP2D6-inhibitor:	0.515
CYP2D6-substrate:	0.084
CYP3A4-inhibitor:	0.224
CYP3A4-substrate:	0.357

ADMET: Excretion

Clearance (CL):	6.843
Half-life (T1/2):	0.453

ADMET: Toxicity

hERG Blockers:	0.185
Human Hepatotoxicity (H-HT):	0.347
Drug-inuced Liver Injury (DILI):	0.921
AMES Toxicity:	0.023
Rat Oral Acute Toxicity:	0.963
Maximum Recommended Daily Dose:	0.944
Skin Sensitization:	0.928
Carcinogencity:	0.36
Eye Corrosion:	0.981
Eye Irritation:	0.352
Respiratory Toxicity:	0.984

Download Data

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

Natural Product: NPC324944

Natural Product ID:	NPC324944
*Common Name:**	(1S,3Ar,3A1S,4S,6S,6As,9Ar)-1-Isocyano-6-(2-Isocyano-2-Methylpropyl)-1,4-Dimethyl-7-Methylenedodecahydro-1H-Phenalene
IUPAC Name:	(1S,3S,3aR,6S,6aR,9aS,9bS)-6-isocyano-1-(2-isocyano-2-methylpropyl)-3,6-dimethyl-9-methylidene-2,3,3a,4,5,6a,7,8,9a,9b-decahydro-1H-phenalene
Synonyms:	7,15-Diisocyano-11(20)-amphilectene
Standard InCHIKey:	OVPVEBDXXUVHDQ-FASAMWFTSA-N
Standard InCHI:	InChI=1S/C22H32N2/c1-14-8-9-18-20-17(10-11-22(18,5)24-7)15(2)12-16(19(14)20)13-21(3,4)23-6/h15-20H,1,8-13H2,2-5H3/t15-,16-,17+,18+,19-,20+,22-/m0/s1
SMILES:	CC1CC(C2C3C1CCC(C3CCC2=C)(C)[N+]#[C-])CC(C)(C)[N+]#[C-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1911840
PubChem CID:	56840669
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	3

Activity Type	# Activity
Cell Line	4
NON-MOLECULAR	4
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	=	3000.0	nM	PMID[556192]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	16000.0	nM	PMID[556192]
NPT114	Cell Line	LoVo	Homo sapiens	GI50	=	3000.0	nM	PMID[556192]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	GI50	=	32000.0	nM	PMID[556192]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	10000.0	nM	PMID[556192]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	4000.0	nM	PMID[556192]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[556193]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	200.0	nM	PMID[556193]
NPT27	Others	Unspecified		IC50	>	10000.0	nM	PMID[556193]

☑ 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 NPC324944 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	360
0.1-0.2	12260
0.2-0.3	19664
0.3-0.4	8018
0.4-0.5	2137
0.5-0.6	192
0.6-0.7	38
0.7-0.8	20
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	NPC173815
0.963	High Similarity	NPC318036
0.8966	High Similarity	NPC317778
0.8214	Intermediate Similarity	NPC212905
0.8125	Intermediate Similarity	NPC476135
0.7969	Intermediate Similarity	NPC474456
0.7869	Intermediate Similarity	NPC28755
0.7869	Intermediate Similarity	NPC152211
0.7647	Intermediate Similarity	NPC476329
0.7612	Intermediate Similarity	NPC138409
0.7612	Intermediate Similarity	NPC184919
0.7541	Intermediate Similarity	NPC470370
0.7541	Intermediate Similarity	NPC470369
0.75	Intermediate Similarity	NPC145715
0.7458	Intermediate Similarity	NPC474416
0.7385	Intermediate Similarity	NPC473959
0.7222	Intermediate Similarity	NPC476308
0.7121	Intermediate Similarity	NPC476682
0.7077	Intermediate Similarity	NPC219621
0.6984	Remote Similarity	NPC474457
0.697	Remote Similarity	NPC474435
0.697	Remote Similarity	NPC474027
0.697	Remote Similarity	NPC475755
0.6949	Remote Similarity	NPC476681
0.6944	Remote Similarity	NPC476904
0.6901	Remote Similarity	NPC21773
0.6769	Remote Similarity	NPC474420
0.6769	Remote Similarity	NPC474455
0.6769	Remote Similarity	NPC472827
0.6769	Remote Similarity	NPC474454
0.6719	Remote Similarity	NPC474528
0.6719	Remote Similarity	NPC475696
0.6719	Remote Similarity	NPC474415
0.6716	Remote Similarity	NPC89921
0.6711	Remote Similarity	NPC211322
0.6667	Remote Similarity	NPC265789
0.6667	Remote Similarity	NPC311809
0.6613	Remote Similarity	NPC127944
0.6607	Remote Similarity	NPC193180
0.6533	Remote Similarity	NPC7214
0.6515	Remote Similarity	NPC475716
0.6515	Remote Similarity	NPC21781
0.65	Remote Similarity	NPC22765
0.6479	Remote Similarity	NPC476288
0.6429	Remote Similarity	NPC37792
0.6429	Remote Similarity	NPC103290
0.6406	Remote Similarity	NPC469770
0.64	Remote Similarity	NPC125828
0.6329	Remote Similarity	NPC329782
0.625	Remote Similarity	NPC476683
0.625	Remote Similarity	NPC472312
0.623	Remote Similarity	NPC17518
0.6203	Remote Similarity	NPC12035
0.6173	Remote Similarity	NPC171639
0.6154	Remote Similarity	NPC79704
0.6145	Remote Similarity	NPC157479
0.6145	Remote Similarity	NPC474458
0.6143	Remote Similarity	NPC53276
0.6125	Remote Similarity	NPC118329
0.6125	Remote Similarity	NPC152039
0.6071	Remote Similarity	NPC43308
0.6066	Remote Similarity	NPC124851
0.6056	Remote Similarity	NPC469970
0.6049	Remote Similarity	NPC283277
0.6049	Remote Similarity	NPC215474
0.6034	Remote Similarity	NPC105246
0.6034	Remote Similarity	NPC190232
0.6027	Remote Similarity	NPC271640
0.6024	Remote Similarity	NPC147513
0.6024	Remote Similarity	NPC152684
0.6	Remote Similarity	NPC474086
0.6	Remote Similarity	NPC250632
0.5952	Remote Similarity	NPC56107
0.5926	Remote Similarity	NPC90150
0.5926	Remote Similarity	NPC257962
0.5909	Remote Similarity	NPC123194
0.5846	Remote Similarity	NPC472828
0.5833	Remote Similarity	NPC202189
0.5833	Remote Similarity	NPC311769
0.5833	Remote Similarity	NPC24733
0.5833	Remote Similarity	NPC182106
0.5814	Remote Similarity	NPC259252
0.5775	Remote Similarity	NPC472544
0.5738	Remote Similarity	NPC86683
0.5733	Remote Similarity	NPC245223
0.5733	Remote Similarity	NPC124384
0.5733	Remote Similarity	NPC472831
0.5732	Remote Similarity	NPC475724
0.5732	Remote Similarity	NPC474122
0.5714	Remote Similarity	NPC106990
0.569	Remote Similarity	NPC62086
0.569	Remote Similarity	NPC78551
0.569	Remote Similarity	NPC227632
0.5667	Remote Similarity	NPC192529
0.5658	Remote Similarity	NPC120167
0.5658	Remote Similarity	NPC473442
0.5652	Remote Similarity	NPC472830
0.5652	Remote Similarity	NPC469769
0.5652	Remote Similarity	NPC231129
0.5616	Remote Similarity	NPC476737
0.5616	Remote Similarity	NPC27243
0.5606	Remote Similarity	NPC476679

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 NPC324944 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	268
0.1-0.2	3105
0.2-0.3	4505
0.3-0.4	1097
0.4-0.5	157
0.5-0.6	14
0.6-0.7	4
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
0.6667	Remote Similarity	NPD5365	Phase 2
0.614	Remote Similarity	NPD346	Approved
0.614	Remote Similarity	NPD347	Approved
0.6102	Remote Similarity	NPD873	Approved
0.6102	Remote Similarity	NPD871	Approved
0.6034	Remote Similarity	NPD1799	Clinical (unspecified phase)
0.5867	Remote Similarity	NPD6939	Phase 2
0.5867	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