NPASS Compound

Structure

NPC487745 OpenBabel06302216202D 38 44 0 0 1 0 0 0 0 0999 V2000 1.3844 4.9350 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3782 5.0405 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2162 4.2219 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1955 3.2978 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3989 2.4792 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3729 2.5813 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9484 1.7889 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5498 0.8943 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5758 0.7922 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0004 1.5846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9311 1.2822 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7780 1.7715 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6263 1.2826 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4743 1.7719 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3226 1.2830 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3229 0.3037 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4748 -0.1856 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4746 0.7931 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4750 -1.1656 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3233 -1.6544 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1714 -1.1652 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1712 -0.1852 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 6.0186 0.3041 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.8663 -0.1848 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.8666 -1.1647 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.7141 -1.6539 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5616 -2.1431 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5615 -1.1645 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2249 -2.5015 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0191 -1.6540 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7322 0.3155 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1712 0.7934 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6265 0.3033 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6268 -0.6967 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9313 0.3029 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.3231 -0.6757 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0335 5.9645 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 2 0 0 0 0 2 38 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 10 2 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 7 8 1 0 0 0 0 8 9 2 0 0 0 0 9 36 1 0 0 0 0 9 10 1 0 0 0 0 10 11 1 0 0 0 0 11 35 2 0 0 0 0 11 12 1 0 0 0 0 13 12 1 6 0 0 0 13 14 1 0 0 0 0 13 33 1 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 16 22 1 0 0 0 0 16 17 1 0 0 0 0 16 37 1 6 0 0 0 17 18 1 1 0 0 0 17 19 1 0 0 0 0 17 33 1 0 0 0 0 19 20 1 0 0 0 0 21 20 1 1 0 0 0 21 22 1 0 0 0 0 21 30 1 0 0 0 0 22 32 1 6 0 0 0 22 23 1 0 0 0 0 23 24 1 0 0 0 0 23 32 1 6 0 0 0 24 25 1 0 0 0 0 24 31 1 6 0 0 0 25 26 1 1 0 0 0 25 30 1 0 0 0 0 26 27 1 0 0 0 0 26 28 1 0 0 0 0 26 29 1 0 0 0 0 33 34 1 6 0 0 0 33 35 1 0 0 0 0 35 36 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	521.31
Volume:	543.898
LogP:	5.51
LogD:	3.584
LogS:	-4.437
# Rotatable Bonds:	3
TPSA:	98.24
# H-Bond Aceptor:	6
# H-Bond Donor:	4
# Rings:	7
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.353
Synthetic Accessibility Score:	5.725
Fsp3:	0.688
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.941
MDCK Permeability:	1.2601919479493517e-05
Pgp-inhibitor:	0.968
Pgp-substrate:	0.99
Human Intestinal Absorption (HIA):	0.038
20% Bioavailability (F20%):	0.821
30% Bioavailability (F30%):	0.197

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.649
Plasma Protein Binding (PPB):	93.8829574584961%
Volume Distribution (VD):	1.596
Pgp-substrate:	5.237822532653809%

ADMET: Metabolism

CYP1A2-inhibitor:	0.167
CYP1A2-substrate:	0.692
CYP2C19-inhibitor:	0.211
CYP2C19-substrate:	0.632
CYP2C9-inhibitor:	0.392
CYP2C9-substrate:	0.065
CYP2D6-inhibitor:	0.399
CYP2D6-substrate:	0.371
CYP3A4-inhibitor:	0.705
CYP3A4-substrate:	0.352

ADMET: Excretion

Clearance (CL):	12.139
Half-life (T1/2):	0.111

ADMET: Toxicity

hERG Blockers:	0.89
Human Hepatotoxicity (H-HT):	0.89
Drug-inuced Liver Injury (DILI):	0.046
AMES Toxicity:	0.017
Rat Oral Acute Toxicity:	0.968
Maximum Recommended Daily Dose:	0.938
Skin Sensitization:	0.328
Carcinogencity:	0.937
Eye Corrosion:	0.003
Eye Irritation:	0.012
Respiratory Toxicity:	0.988

Download Data

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

Natural Product: NPC487745

Natural Product ID:	NPC487745
*Common Name:**	RQTDORUGVRDBLB-WQRLADHGSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	RQTDORUGVRDBLB-WQRLADHGSA-N
Standard InCHI:	InChI=1S/C32H43NO5/c1-17(2)10-11-18-8-7-9-21-23(18)20-16-19-12-15-31(36)29(5,30(19,6)25(20)33-21)14-13-22-32(31)27(38-32)24(34)26(37-22)28(3,4)35/h7-10,19,22,24,26-27,33-36H,11-16H2,1-6H3/t19-,22-,24+,26-,27+,29+,30+,31-,32-/m0/s1
SMILES:	CC(=CCc1cccc2c1c1C[C@@H]3CC[C@@]4([C@](C)(CC[C@H]5[C@@]64[C@@H]([C@@H]([C@@H](C(C)(C)O)O5)O)O6)[C@@]3(C)c1[nH]2)O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001640] Naphthopyrans

*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
NPO41068	Tolypocladium sp. XL115	Strain	Ophiocordycipitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30702286]

☑ 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	7
MIC	9

Activity Type	# Activity
Cell Line	4
CELL-LINE	2
ORGANISM	8
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	IC50	=	16320.0	nM	PMID[30702286]
NPT1229	Cell Line	Huh-7	Homo sapiens	IC50	=	16320.0	nM	PMID[30702286]
NPT114	Cell Line	LoVo	Homo sapiens	IC50	=	16320.0	nM	PMID[30702286]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	16320.0	nM	PMID[30702286]
NPT15189	ORGANISM	Alternaria fragaria	Alternaria fragaria	MIC	=	6.25	ug.mL-1	PMID[30702286]
NPT5409	Organism	Corynespora cassiicola	Corynespora cassiicola	MIC	=	6.25	ug.mL-1	PMID[30702286]
NPT962	Organism	Alternaria alternata	Alternaria alternata	MIC	=	6.25	ug.mL-1	PMID[30702286]
NPT635	Organism	Botryotinia fuckeliana	Botryotinia fuckeliana	MIC	=	6.25	ug.mL-1	PMID[30702286]
NPT2	Others	Unspecified		MIC	=	6.25	ug.mL-1	PMID[30702286]
NPT1503	Organism	Verticillium dahliae	Verticillium dahliae	MIC	=	6.25	ug.mL-1	PMID[30702286]
NPT638	Organism	Sclerotinia sclerotiorum	Sclerotinia sclerotiorum	MIC	=	6.25	ug.mL-1	PMID[30702286]
NPT314	Organism	Bacillus cereus	Bacillus cereus	MIC	=	25.0	ug.mL-1	PMID[30702286]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	12.5	ug.mL-1	PMID[30702286]
NPT21748	CELL-LINE	LN-229	Homo sapiens	IC50	=	16320.0	nM	PMID[30702286]
NPT2	Others	Unspecified		IC50	=	16320.0	nM	PMID[30702286]
NPT26526	CELL-LINE	MHCC97H	Homo sapiens	IC50	=	16320.0	nM	PMID[30702286]

☑ 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 NPC487745 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	447
0.1-0.2	1709
0.2-0.3	5744
0.3-0.4	20733
0.4-0.5	10072
0.5-0.6	2749
0.6-0.7	1066
0.7-0.8	132
0.8-0.85	24
0.85-0.9	12
0.9-0.95	5
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID

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 NPC487745 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	276
0.1-0.2	550
0.2-0.3	712
0.3-0.4	2650
0.4-0.5	3369
0.5-0.6	1318
0.6-0.7	268
0.7-0.8	7
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

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