NPASS Compound

Structure

NPC481448 OpenBabel06302216002D 27 32 0 0 1 0 0 0 0 0999 V2000 -2.5999 -3.2446 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4671 -2.7436 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.4668 -1.7664 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3129 -1.2776 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1593 -1.7660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0050 -1.2774 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8514 -1.7658 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8517 -2.7430 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0061 -3.2316 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1596 -2.7432 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3135 -3.2320 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -4.3138 -4.2092 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7396 -4.9999 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8522 -4.6961 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6978 -4.2076 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6981 -3.2314 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3129 -0.3009 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4668 0.1870 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6206 -0.3018 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7748 0.1865 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9289 -0.3018 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9289 -1.2785 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7748 -1.7669 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6206 -1.2785 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.5804 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5741 -0.7902 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 11 1 0 0 0 0 2 3 1 0 0 0 0 3 24 2 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 4 17 2 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 16 1 0 0 0 0 8 9 2 0 0 0 0 9 10 1 0 0 0 0 9 14 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 13 1 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 17 18 1 0 0 0 0 18 19 2 0 0 0 0 19 24 1 0 0 0 0 19 20 1 0 0 0 0 20 21 2 0 0 0 0 21 27 1 0 0 0 0 21 22 1 0 0 0 0 22 23 2 0 0 0 0 22 25 1 0 0 0 0 23 24 1 0 0 0 0 25 26 1 0 0 0 0 26 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	363.11
Volume:	354.29
LogP:	4.525
LogD:	3.361
LogS:	-7.15
# Rotatable Bonds:	1
TPSA:	49.39
# H-Bond Aceptor:	6
# H-Bond Donor:	0
# Rings:	6
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.65
Synthetic Accessibility Score:	3.399
Fsp3:	0.238
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.8
MDCK Permeability:	5.0447524699848145e-05
Pgp-inhibitor:	0.477
Pgp-substrate:	0.64
Human Intestinal Absorption (HIA):	0.001
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.062

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.072
Plasma Protein Binding (PPB):	96.1535415649414%
Volume Distribution (VD):	0.599
Pgp-substrate:	0.8925045132637024%

ADMET: Metabolism

CYP1A2-inhibitor:	0.977
CYP1A2-substrate:	0.306
CYP2C19-inhibitor:	0.971
CYP2C19-substrate:	0.215
CYP2C9-inhibitor:	0.757
CYP2C9-substrate:	0.891
CYP2D6-inhibitor:	0.981
CYP2D6-substrate:	0.9
CYP3A4-inhibitor:	0.872
CYP3A4-substrate:	0.176

ADMET: Excretion

Clearance (CL):	14.959
Half-life (T1/2):	0.096

ADMET: Toxicity

hERG Blockers:	0.052
Human Hepatotoxicity (H-HT):	0.059
Drug-inuced Liver Injury (DILI):	0.917
AMES Toxicity:	0.873
Rat Oral Acute Toxicity:	0.092
Maximum Recommended Daily Dose:	0.894
Skin Sensitization:	0.85
Carcinogencity:	0.969
Eye Corrosion:	0.003
Eye Irritation:	0.075
Respiratory Toxicity:	0.914

Download Data

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

Natural Product: NPC481448

Natural Product ID:	NPC481448
*Common Name:**	MHPDDMNAUJQRSW-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	MHPDDMNAUJQRSW-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C21H17NO5/c1-22-19-13(4-3-11-7-16-17(8-14(11)19)26-9-25-16)12-5-6-15-20(27-10-24-15)18(12)21(22)23-2/h3-8,21H,9-10H2,1-2H3
SMILES:	CN1c2c(-c3ccc4c(c3C1OC)OCO4)ccc1cc3c(cc21)OCO3
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	14847270
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002665] Benzophenanthridine alkaloids [CHEMONTID:0002667] Dihydrobenzophenanthridine alkaloids

*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
NPO5305	Corydalis mucronifera	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29400966]
NPO5305	Corydalis mucronifera	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5305	Corydalis mucronifera	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5305	Corydalis mucronifera	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5305	Corydalis mucronifera	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ 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	2
Individual Protein	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT204	Individual Protein	Acetylcholinesterase	Homo sapiens	IC50	=	96800.0	nM	PMID[29400966]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	1590.0	nM	PMID[33479636]
NPT2341	Cell Line	NCI-H1975	Homo sapiens	IC50	=	1170.0	nM	PMID[33479636]

☑ 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 NPC481448 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	472
0.1-0.2	2362
0.2-0.3	10770
0.3-0.4	6770
0.4-0.5	9708
0.5-0.6	10354
0.6-0.7	1628
0.7-0.8	564
0.8-0.85	50
0.85-0.9	9
0.9-0.95	5
0.95-1	5

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 NPC481448 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	254
0.1-0.2	804
0.2-0.3	1012
0.3-0.4	1755
0.4-0.5	2901
0.5-0.6	1938
0.6-0.7	446
0.7-0.8	40
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