NPASS Compound

Structure

NPC273374 OpenBabel06302215512D 27 30 0 0 1 0 0 0 0 0999 V2000 -2.5775 0.4810 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7048 -0.0232 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8318 0.4805 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8316 1.4412 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0005 1.9213 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 0.0007 2.8826 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8327 3.3628 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6650 2.8822 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3294 2.8819 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1619 3.3621 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9937 2.8816 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9935 1.9203 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1615 1.4401 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3292 1.9206 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4972 1.4404 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.6648 1.9210 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8323 1.4408 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8321 0.4801 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 -0.0003 -1.0079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8732 -1.5116 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7459 -1.0074 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6189 -1.5111 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8724 -1.5120 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8722 -2.5199 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7454 -1.0083 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6181 -1.5125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 0 0 0 3 2 1 1 0 0 0 3 4 1 0 0 0 0 3 19 1 0 0 0 0 4 5 1 0 0 0 0 5 17 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 8 16 2 0 0 0 0 8 9 1 0 0 0 0 9 14 2 0 0 0 0 9 10 1 0 0 0 0 10 11 2 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 16 17 1 0 0 0 0 17 18 1 6 0 0 0 18 19 1 0 0 0 0 19 20 1 6 0 0 0 20 21 2 0 0 0 0 20 24 1 0 0 0 0 21 22 1 0 0 0 0 22 23 1 0 0 0 0 24 25 2 0 0 0 0 24 26 1 0 0 0 0 26 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	366.19
Volume:	384.751
LogP:	3.704
LogD:	3.433
LogS:	-3.904
# Rotatable Bonds:	5
TPSA:	54.56
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.389
Synthetic Accessibility Score:	3.991
Fsp3:	0.409
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.886
MDCK Permeability:	2.427685285510961e-05
Pgp-inhibitor:	0.989
Pgp-substrate:	0.269
Human Intestinal Absorption (HIA):	0.011
20% Bioavailability (F20%):	0.052
30% Bioavailability (F30%):	0.024

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.988
Plasma Protein Binding (PPB):	86.89885711669922%
Volume Distribution (VD):	1.332
Pgp-substrate:	12.089208602905273%

ADMET: Metabolism

CYP1A2-inhibitor:	0.921
CYP1A2-substrate:	0.943
CYP2C19-inhibitor:	0.822
CYP2C19-substrate:	0.838
CYP2C9-inhibitor:	0.617
CYP2C9-substrate:	0.204
CYP2D6-inhibitor:	0.949
CYP2D6-substrate:	0.865
CYP3A4-inhibitor:	0.928
CYP3A4-substrate:	0.893

ADMET: Excretion

Clearance (CL):	3.979
Half-life (T1/2):	0.386

ADMET: Toxicity

hERG Blockers:	0.922
Human Hepatotoxicity (H-HT):	0.46
Drug-inuced Liver Injury (DILI):	0.717
AMES Toxicity:	0.163
Rat Oral Acute Toxicity:	0.959
Maximum Recommended Daily Dose:	0.991
Skin Sensitization:	0.658
Carcinogencity:	0.959
Eye Corrosion:	0.004
Eye Irritation:	0.03
Respiratory Toxicity:	0.983

Download Data

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

Natural Product: NPC273374

Natural Product ID:	NPC273374
*Common Name:**	TZUGIFAYWNNSAO-XPOGPMDLSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	TZUGIFAYWNNSAO-XPOGPMDLSA-N
Standard InCHI:	InChI=1S/C22H26N2O3/c1-4-14-12-24-10-9-16-15-7-5-6-8-19(15)23-21(16)20(24)11-17(14)18(13-26-2)22(25)27-3/h4-8,13-14,17,20,23H,1,9-12H2,2-3H3/b18-13+/t14-,17-,20-/m0/s1
SMILES:	C=C[C@H]1CN2CCc3c4ccccc4[nH]c3[C@@H]2C[C@@H]1/C(=COC)/C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	3037997
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002750] Corynanthean-type 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
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10869194]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	leaves	n.a.	n.a.	PMID[18588343]
NPO3656	Ardisia pusilla	Species	Primulaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[19039733]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19331340]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21070010]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21070010]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27700077]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28225280]
NPO40904	Pausinystalia yohimbe	Species	n.a.	n.a.	Bark	n.a.	n.a.	PMID[30059216]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31789520]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31804070]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3656	Ardisia pusilla	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6211	Rosa gallica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3656	Ardisia pusilla	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6211	Rosa gallica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO3656	Ardisia pusilla	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8571	Actinostemma lobatum	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8978	Stenocarpus salignus	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3656	Ardisia pusilla	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2724	Excoecaria cochinchinensis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2200	Ulmus davidiana	Species	Ulmaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10604	Monochaetia dimorphospora	Species	Sporocadaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4870	Stephanitis pyri	Species	Tingidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6211	Rosa gallica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3135	Dendrobium lohohense	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4229	Glossocarya calcicola	Species	Lamiaceae	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
EC50	1
IC50	2

Activity Type	# Activity
Cell Line	1
CELL-LINE	1
Individual Protein	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4372	Cell Line	Murine T-cell line	Mus musculus	IC50	=	16800.0	nM	PMID[30059216]
NPT92	Individual Protein	Serotonin 1a (5-HT1a) receptor	Homo sapiens	EC50	>	100000.0	nM	PMID[31789520]
NPT27699	CELL-LINE	B-cell line	Mus musculus	IC50	=	13500.0	nM	PMID[30059216]

☑ 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 NPC273374 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	288
0.1-0.2	1707
0.2-0.3	9230
0.3-0.4	20466
0.4-0.5	5698
0.5-0.6	2497
0.6-0.7	1982
0.7-0.8	706
0.8-0.85	72
0.85-0.9	25
0.9-0.95	15
0.95-1	11

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 NPC273374 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	177
0.1-0.2	505
0.2-0.3	692
0.3-0.4	1348
0.4-0.5	2482
0.5-0.6	2679
0.6-0.7	1088
0.7-0.8	173
0.8-0.85	1
0.85-0.9	3
0.9-0.95	2
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