NPASS Compound

Structure

NPC97336 OpenBabel07101719152D 26 31 0 0 1 0 0 0 0 0999 V2000 -2.3392 4.1566 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8705 1.5761 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1327 -0.1120 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6351 -0.7968 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6351 0.5729 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2053 3.0430 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0748 0.9973 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3203 2.1923 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4990 1.6178 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3638 -0.5352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7487 2.4223 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1021 3.1851 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1768 2.8059 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8300 -0.5352 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8300 0.3113 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3638 0.3113 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0969 -0.9585 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8253 0.1884 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0969 0.7345 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2516 1.8087 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5758 0.6205 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3263 1.4295 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2231 1.5716 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -2.0969 -1.9585 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5055 -0.5447 0.0000 O 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 2 21 1 0 0 0 0 3 4 1 0 0 0 0 3 5 1 0 0 0 0 6 8 1 0 0 0 0 7 9 1 0 0 0 0 7 18 1 0 0 0 0 9 22 1 0 0 0 0 10 16 1 0 0 0 0 10 17 1 0 0 0 0 11 12 1 0 0 0 0 11 23 1 0 0 0 0 12 1 1 1 0 0 0 12 13 1 0 0 0 0 13 6 1 1 0 0 0 13 20 1 0 0 0 0 14 4 1 1 0 0 0 14 15 1 0 0 0 0 14 17 1 0 0 0 0 15 5 1 1 0 0 0 15 19 1 0 0 0 0 16 19 1 0 0 0 0 16 21 1 1 0 0 0 17 24 2 0 0 0 0 18 25 2 0 0 0 0 18 26 1 0 0 0 0 19 23 1 6 0 0 0 20 22 1 1 0 0 0 20 23 1 0 0 0 0 21 22 1 1 0 0 0 21 26 1 0 0 0 0 22 8 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	357.23
Volume:	369.824
LogP:	3.803
LogD:	3.535
LogS:	-4.355
# Rotatable Bonds:	0
TPSA:	46.61
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	6
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.625
Synthetic Accessibility Score:	5.729
Fsp3:	0.909
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:	-4.798
MDCK Permeability:	3.674194886116311e-05
Pgp-inhibitor:	0.01
Pgp-substrate:	0.126
Human Intestinal Absorption (HIA):	0.025
20% Bioavailability (F20%):	0.084
30% Bioavailability (F30%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.685
Plasma Protein Binding (PPB):	66.7702865600586%
Volume Distribution (VD):	0.586
Pgp-substrate:	17.747112274169922%

ADMET: Metabolism

CYP1A2-inhibitor:	0.049
CYP1A2-substrate:	0.245
CYP2C19-inhibitor:	0.053
CYP2C19-substrate:	0.897
CYP2C9-inhibitor:	0.064
CYP2C9-substrate:	0.065
CYP2D6-inhibitor:	0.215
CYP2D6-substrate:	0.807
CYP3A4-inhibitor:	0.861
CYP3A4-substrate:	0.905

ADMET: Excretion

Clearance (CL):	20.303
Half-life (T1/2):	0.616

ADMET: Toxicity

hERG Blockers:	0.089
Human Hepatotoxicity (H-HT):	0.445
Drug-inuced Liver Injury (DILI):	0.656
AMES Toxicity:	0.036
Rat Oral Acute Toxicity:	0.821
Maximum Recommended Daily Dose:	0.908
Skin Sensitization:	0.456
Carcinogencity:	0.678
Eye Corrosion:	0.092
Eye Irritation:	0.057
Respiratory Toxicity:	0.971

Download Data

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

Natural Product: NPC97336

Natural Product ID:	NPC97336
*Common Name:**	Daphnioldhanine J
IUPAC Name:	n.a.
Synonyms:	Daphnioldhanine J
Standard InCHIKey:	XWNUAACCLIULKG-NMOPZWIYSA-N
Standard InCHI:	InChI=1S/C22H31NO3/c1-12-11-23-19-15-5-3-4-14(15)17(24)10-16(19)21(2)22(9-7-18(25)26-21)8-6-13(12)20(22)23/h12-16,19-20H,3-11H2,1-2H3/t12-,13-,14+,15-,16+,19+,20+,21+,22+/m1/s1
SMILES:	O=C1CC[C@@]23[C@](O1)(C)[C@H]1CC(=O)[C@@H]4[C@H]([C@@H]1N1[C@H]3[C@H](CC2)[C@@H](C1)C)CCC4
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL465875
PubChem CID:	24850198
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0003787] Quinolidines

*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
NPO32797	daphniphyllum oldhami	Species	Daphniphyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18288811]
NPO32797	daphniphyllum oldhami	Species	Daphniphyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19441852]

☑ 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
Others	1

Activity Type	# Activity
CELL-LINE	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20967	CELL-LINE	Platelet	n.a.	Inhibition	=	71.6	%	PMID[517599]

☑ 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 NPC97336 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	264
0.1-0.2	4675
0.2-0.3	18317
0.3-0.4	11533
0.4-0.5	6611
0.5-0.6	1160
0.6-0.7	124
0.7-0.8	12
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.719	Intermediate Similarity	NPC473477
0.7179	Intermediate Similarity	NPC470538
0.7059	Intermediate Similarity	NPC96731
0.696	Remote Similarity	NPC212106
0.6875	Remote Similarity	NPC233274
0.6875	Remote Similarity	NPC287638
0.6875	Remote Similarity	NPC194750
0.6807	Remote Similarity	NPC135431
0.675	Remote Similarity	NPC209252
0.6748	Remote Similarity	NPC238323
0.6746	Remote Similarity	NPC280903
0.6614	Remote Similarity	NPC470537
0.6574	Remote Similarity	NPC312637
0.6471	Remote Similarity	NPC216090
0.646	Remote Similarity	NPC220111
0.6429	Remote Similarity	NPC197701
0.64	Remote Similarity	NPC88190
0.6343	Remote Similarity	NPC474210
0.6321	Remote Similarity	NPC277918
0.626	Remote Similarity	NPC470539
0.624	Remote Similarity	NPC476952
0.621	Remote Similarity	NPC476955
0.621	Remote Similarity	NPC476502
0.621	Remote Similarity	NPC471846
0.621	Remote Similarity	NPC39041
0.621	Remote Similarity	NPC202722
0.621	Remote Similarity	NPC241294
0.621	Remote Similarity	NPC471845
0.6198	Remote Similarity	NPC63511
0.6195	Remote Similarity	NPC174117
0.6182	Remote Similarity	NPC135005
0.614	Remote Similarity	NPC471843
0.6134	Remote Similarity	NPC195841
0.6134	Remote Similarity	NPC233256
0.6107	Remote Similarity	NPC476951
0.6095	Remote Similarity	NPC1882
0.6091	Remote Similarity	NPC203170
0.6083	Remote Similarity	NPC48127
0.6083	Remote Similarity	NPC8009
0.6083	Remote Similarity	NPC267217
0.6083	Remote Similarity	NPC83047
0.6068	Remote Similarity	NPC474348
0.6066	Remote Similarity	NPC470527
0.6066	Remote Similarity	NPC470530
0.6066	Remote Similarity	NPC470531
0.6066	Remote Similarity	NPC470533
0.6066	Remote Similarity	NPC470529
0.6066	Remote Similarity	NPC470528
0.6066	Remote Similarity	NPC470532
0.6048	Remote Similarity	NPC28224
0.604	Remote Similarity	NPC248567
0.6038	Remote Similarity	NPC472230
0.6038	Remote Similarity	NPC472229
0.6033	Remote Similarity	NPC470535
0.6018	Remote Similarity	NPC469998
0.6016	Remote Similarity	NPC470534
0.6	Remote Similarity	NPC86906
0.5985	Remote Similarity	NPC476501
0.5984	Remote Similarity	NPC470536
0.5983	Remote Similarity	NPC128698
0.5983	Remote Similarity	NPC239768
0.5969	Remote Similarity	NPC476504
0.5954	Remote Similarity	NPC476503
0.5946	Remote Similarity	NPC237535
0.594	Remote Similarity	NPC476497
0.5935	Remote Similarity	NPC139778
0.592	Remote Similarity	NPC477963
0.5917	Remote Similarity	NPC475239
0.5917	Remote Similarity	NPC119329
0.5915	Remote Similarity	NPC956
0.5893	Remote Similarity	NPC323156
0.5882	Remote Similarity	NPC470592
0.5868	Remote Similarity	NPC471844
0.5865	Remote Similarity	NPC471046
0.5833	Remote Similarity	NPC265094
0.5818	Remote Similarity	NPC34811
0.5814	Remote Similarity	NPC35037
0.5806	Remote Similarity	NPC473232
0.5778	Remote Similarity	NPC309249
0.576	Remote Similarity	NPC79238
0.5758	Remote Similarity	NPC84562
0.5752	Remote Similarity	NPC473039
0.5752	Remote Similarity	NPC200580
0.5745	Remote Similarity	NPC88943
0.5741	Remote Similarity	NPC58631
0.5739	Remote Similarity	NPC472237
0.5739	Remote Similarity	NPC472238
0.5727	Remote Similarity	NPC101138
0.5727	Remote Similarity	NPC25802
0.5727	Remote Similarity	NPC82492
0.5727	Remote Similarity	NPC51135
0.5726	Remote Similarity	NPC473994
0.5714	Remote Similarity	NPC476498
0.5704	Remote Similarity	NPC478136
0.5701	Remote Similarity	NPC118987
0.5692	Remote Similarity	NPC475340
0.5688	Remote Similarity	NPC13494
0.5688	Remote Similarity	NPC258153
0.5688	Remote Similarity	NPC476458
0.5664	Remote Similarity	NPC322966
0.5659	Remote Similarity	NPC221196
0.5659	Remote Similarity	NPC39485
0.5649	Remote Similarity	NPC470593
0.5649	Remote Similarity	NPC470594
0.5648	Remote Similarity	NPC125366
0.5648	Remote Similarity	NPC170038
0.5631	Remote Similarity	NPC110615
0.5625	Remote Similarity	NPC92139
0.5625	Remote Similarity	NPC476499
0.562	Remote Similarity	NPC476755
0.5619	Remote Similarity	NPC155441
0.5615	Remote Similarity	NPC475887

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 NPC97336 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	153
0.1-0.2	1910
0.2-0.3	4898
0.3-0.4	1610
0.4-0.5	438
0.5-0.6	126
0.6-0.7	15
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
0.6552	Remote Similarity	NPD6920	Discontinued
0.6471	Remote Similarity	NPD7155	Clinical (unspecified phase)
0.632	Remote Similarity	NPD7517	Approved
0.632	Remote Similarity	NPD7519	Approved
0.632	Remote Similarity	NPD7518	Approved
0.6283	Remote Similarity	NPD5349	Clinical (unspecified phase)
0.6271	Remote Similarity	NPD8040	Discontinued
0.6102	Remote Similarity	NPD7911	Approved
0.6102	Remote Similarity	NPD7912	Approved
0.6102	Remote Similarity	NPD7986	Approved
0.6102	Remote Similarity	NPD7987	Approved
0.6061	Remote Similarity	NPD2697	Approved
0.6061	Remote Similarity	NPD2694	Approved
0.6061	Remote Similarity	NPD2696	Approved
0.6061	Remote Similarity	NPD2695	Approved
0.6033	Remote Similarity	NPD6415	Discontinued
0.5982	Remote Similarity	NPD6934	Discontinued
0.595	Remote Similarity	NPD7990	Approved
0.595	Remote Similarity	NPD7989	Approved
0.595	Remote Similarity	NPD7646	Clinical (unspecified phase)
0.5922	Remote Similarity	NPD3702	Approved
0.5915	Remote Similarity	NPD5193	Discontinued
0.5847	Remote Similarity	NPD8418	Phase 2
0.584	Remote Similarity	NPD8077	Approved
0.584	Remote Similarity	NPD8078	Approved
0.5827	Remote Similarity	NPD7755	Approved
0.5827	Remote Similarity	NPD7754	Approved
0.5703	Remote Similarity	NPD6940	Discontinued
0.5669	Remote Similarity	NPD8298	Phase 2
0.5631	Remote Similarity	NPD5777	Approved
0.563	Remote Similarity	NPD3102	Approved
0.563	Remote Similarity	NPD3103	Approved
0.563	Remote Similarity	NPD3101	Approved
0.563	Remote Similarity	NPD3104	Approved
0.5607	Remote Similarity	NPD617	Approved
0.56	Remote Similarity	NPD4224	Phase 2

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