NPASS Compound

Structure

CID31344 OpenBabel06191715362D 25 27 0 0 1 0 0 0 0 0999 V2000 -3.4956 2.4939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5171 -0.4916 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7250 0.4865 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3581 -1.7788 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8229 -0.1315 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0981 -3.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7891 -2.0878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5661 -0.8006 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4071 -2.0878 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9819 1.1557 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0308 0.8467 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1898 2.1338 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2877 1.5158 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0981 -3.0388 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 23 1 0 0 0 0 2 24 1 0 0 0 0 3 5 2 0 0 0 0 3 13 1 0 0 0 0 4 6 2 0 0 0 0 4 14 1 0 0 0 0 5 17 1 0 0 0 0 6 18 1 0 0 0 0 7 13 1 0 0 0 0 8 14 1 0 0 0 0 9 13 2 0 0 0 0 9 19 1 0 0 0 0 10 14 2 0 0 0 0 10 20 1 0 0 0 0 11 15 1 0 0 0 0 11 25 1 0 0 0 0 12 16 1 0 0 0 0 12 25 1 0 0 0 0 15 7 1 6 0 0 0 15 16 1 0 0 0 0 16 8 1 1 0 0 0 17 19 2 0 0 0 0 17 21 1 0 0 0 0 18 20 2 0 0 0 0 18 22 1 0 0 0 0 19 23 1 0 0 0 0 20 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	344.16
Volume:	356.939
LogP:	3.083
LogD:	3.024
LogS:	-3.863
# Rotatable Bonds:	6
TPSA:	68.15
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.842
Synthetic Accessibility Score:	3.155
Fsp3:	0.4
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.734
MDCK Permeability:	1.8250180801260285e-05
Pgp-inhibitor:	0.027
Pgp-substrate:	0.76
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.02
30% Bioavailability (F30%):	0.018

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.053
Plasma Protein Binding (PPB):	98.61617279052734%
Volume Distribution (VD):	0.609
Pgp-substrate:	1.816260576248169%

ADMET: Metabolism

CYP1A2-inhibitor:	0.474
CYP1A2-substrate:	0.895
CYP2C19-inhibitor:	0.725
CYP2C19-substrate:	0.608
CYP2C9-inhibitor:	0.766
CYP2C9-substrate:	0.67
CYP2D6-inhibitor:	0.813
CYP2D6-substrate:	0.915
CYP3A4-inhibitor:	0.427
CYP3A4-substrate:	0.76

ADMET: Excretion

Clearance (CL):	12.98
Half-life (T1/2):	0.873

ADMET: Toxicity

hERG Blockers:	0.269
Human Hepatotoxicity (H-HT):	0.272
Drug-inuced Liver Injury (DILI):	0.718
AMES Toxicity:	0.053
Rat Oral Acute Toxicity:	0.034
Maximum Recommended Daily Dose:	0.882
Skin Sensitization:	0.948
Carcinogencity:	0.347
Eye Corrosion:	0.006
Eye Irritation:	0.938
Respiratory Toxicity:	0.91

Download Data

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

Natural Product: NPC31344

Natural Product ID:	NPC31344
*Common Name:**	(-)-3,4-Divanillyltetrahydrofuran
IUPAC Name:	4-[[(3R,4R)-4-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-3-yl]methyl]-2-methoxyphenol
Synonyms:
Standard InCHIKey:	ROGUIJKVZZROIQ-HOTGVXAUSA-N
Standard InCHI:	InChI=1S/C20H24O5/c1-23-19-9-13(3-5-17(19)21)7-15-11-25-12-16(15)8-14-4-6-18(22)20(10-14)24-2/h3-6,9-10,15-16,21-22H,7-8,11-12H2,1-2H3/t15-,16-/m0/s1
SMILES:	COc1cc(ccc1O)C[C@H]1COC[C@@H]1Cc1ccc(c(c1)OC)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL367448
PubChem CID:	9974771
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003424] 9,9'-epoxylignans

*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
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11112781]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	n.a.	Tanzania	n.a.	PMID[11430019]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	root bark	n.a.	n.a.	PMID[12027753]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	leaves	n.a.	n.a.	PMID[12502337]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[153409]
NPO8106	Kadsura heteroclita	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[16557460]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	n.a.	root	n.a.	PMID[17960072]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[17960072]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[21673922]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23265519]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23317005]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23488669]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	seeds	n.a.	n.a.	PMID[26221771]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[27524650]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[29115831]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[31287310]
NPO62	Tetracera asiatica	Species	Dilleniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8106	Kadsura heteroclita	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20434	Tolypocladium ophioglossoides	Species	Ophiocordycipitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15601	Pyrus x bretschneideri	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO62	Tetracera asiatica	Species	Dilleniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO24527	Plazia daphnoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25151	Euphorbia cheiradenia	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6313	Phormidium sp	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO15601	Pyrus x bretschneideri	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15769	Solidago chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20434	Tolypocladium ophioglossoides	Species	Ophiocordycipitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5923	Bidens cernua	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8408	Symphonia globulifera	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3835	Reticulitermes flavipes	Species	Termitoidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2642	Maytenus apurimacensis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6076	Pentzia calva	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO62	Tetracera asiatica	Species	Dilleniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2309	Achillea micrantha	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1019	Citrus hybr	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO783	Pholiota squarrosa	Species	Strophariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3588	Crucianella maritima	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1358	Iris pallida	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8106	Kadsura heteroclita	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8278	Perenniporia ochroleuca	Species	Polyporaceae	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	1
Others	4

Activity Type	# Activity
Individual Protein	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT12	Individual Protein	Human immunodeficiency virus type 1 integrase	Human immunodeficiency virus 1	Inhibition	<	5.0	%	PMID[508115]
NPT895	Individual Protein	Testis-specific androgen-binding protein	Homo sapiens	Ka	=	0.98	10'9/M	PMID[508116]
NPT895	Individual Protein	Testis-specific androgen-binding protein	Homo sapiens	Ka	=	3.2	10'6/M	PMID[508116]
NPT895	Individual Protein	Testis-specific androgen-binding protein	Homo sapiens	IC50	=	2600.0	nM	PMID[508116]

☑ 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 NPC31344 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	314
0.1-0.2	1324
0.2-0.3	3450
0.3-0.4	11506
0.4-0.5	7628
0.5-0.6	5696
0.6-0.7	8787
0.7-0.8	2917
0.8-0.85	751
0.85-0.9	213
0.9-0.95	98
0.95-1	13

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC317769
0.9655	High Similarity	NPC117780
0.9655	High Similarity	NPC56214
0.9655	High Similarity	NPC232316
0.9655	High Similarity	NPC95614
0.9655	High Similarity	NPC165133
0.9655	High Similarity	NPC227217
0.9655	High Similarity	NPC242885
0.9587	High Similarity	NPC129570
0.9587	High Similarity	NPC184733
0.9587	High Similarity	NPC21867
0.9587	High Similarity	NPC282703
0.9587	High Similarity	NPC128208
0.9587	High Similarity	NPC45774
0.9587	High Similarity	NPC11258
0.9576	High Similarity	NPC85488
0.9569	High Similarity	NPC310338
0.9569	High Similarity	NPC281298
0.9508	High Similarity	NPC475875
0.9496	High Similarity	NPC280704
0.9492	High Similarity	NPC38996
0.9492	High Similarity	NPC160380
0.9483	High Similarity	NPC470626
0.9431	High Similarity	NPC187998
0.9431	High Similarity	NPC181079
0.9431	High Similarity	NPC64201
0.9431	High Similarity	NPC257582
0.9431	High Similarity	NPC77040
0.9431	High Similarity	NPC173308
0.9431	High Similarity	NPC174495
0.9431	High Similarity	NPC242807
0.9431	High Similarity	NPC42300
0.9431	High Similarity	NPC153739
0.9431	High Similarity	NPC241522
0.9431	High Similarity	NPC92164
0.9431	High Similarity	NPC145305
0.9431	High Similarity	NPC275950
0.9421	High Similarity	NPC274356
0.9407	High Similarity	NPC207613
0.9397	High Similarity	NPC293619
0.9355	High Similarity	NPC277804
0.9355	High Similarity	NPC476345
0.9355	High Similarity	NPC228346
0.9355	High Similarity	NPC7171
0.9355	High Similarity	NPC161557
0.9355	High Similarity	NPC27843
0.9355	High Similarity	NPC115207
0.9355	High Similarity	NPC158079
0.9355	High Similarity	NPC40432
0.9339	High Similarity	NPC148627
0.9328	High Similarity	NPC343720
0.9328	High Similarity	NPC113865
0.9328	High Similarity	NPC312675
0.9328	High Similarity	NPC473853
0.9328	High Similarity	NPC184651
0.9328	High Similarity	NPC470212
0.9328	High Similarity	NPC54872
0.9328	High Similarity	NPC262156
0.9328	High Similarity	NPC324571
0.9316	High Similarity	NPC474040
0.928	High Similarity	NPC181049
0.928	High Similarity	NPC207400
0.9268	High Similarity	NPC470084
0.9206	High Similarity	NPC169973
0.9206	High Similarity	NPC158331
0.9187	High Similarity	NPC165045
0.9187	High Similarity	NPC118533
0.9187	High Similarity	NPC5428
0.918	High Similarity	NPC29008
0.918	High Similarity	NPC228771
0.918	High Similarity	NPC9067
0.918	High Similarity	NPC266705
0.9174	High Similarity	NPC471693
0.9174	High Similarity	NPC249788
0.9167	High Similarity	NPC127389
0.9167	High Similarity	NPC290451
0.9134	High Similarity	NPC471942
0.9134	High Similarity	NPC49603
0.9134	High Similarity	NPC176814
0.9134	High Similarity	NPC187616
0.9134	High Similarity	NPC67247
0.9134	High Similarity	NPC4982
0.9134	High Similarity	NPC193026
0.9134	High Similarity	NPC5310
0.9134	High Similarity	NPC287745
0.9134	High Similarity	NPC300776
0.9134	High Similarity	NPC68779
0.9127	High Similarity	NPC175067
0.9127	High Similarity	NPC106739
0.9127	High Similarity	NPC4940
0.9127	High Similarity	NPC204215
0.9127	High Similarity	NPC471505
0.9113	High Similarity	NPC307050
0.9113	High Similarity	NPC277458
0.9106	High Similarity	NPC206882
0.9076	High Similarity	NPC311595
0.9076	High Similarity	NPC24474
0.9068	High Similarity	NPC164386
0.9068	High Similarity	NPC86947
0.9062	High Similarity	NPC126409
0.9062	High Similarity	NPC142547
0.9062	High Similarity	NPC99572
0.9062	High Similarity	NPC101624
0.9062	High Similarity	NPC135777
0.9062	High Similarity	NPC184938
0.9052	High Similarity	NPC165106
0.9032	High Similarity	NPC127587
0.9032	High Similarity	NPC106511
0.9024	High Similarity	NPC194519
0.9008	High Similarity	NPC65933
0.9008	High Similarity	NPC172676
0.9008	High Similarity	NPC216929
0.9008	High Similarity	NPC312713
0.9008	High Similarity	NPC57268
0.9008	High Similarity	NPC126935
0.8992	High Similarity	NPC177160
0.8992	High Similarity	NPC474214
0.8992	High Similarity	NPC77861
0.8992	High Similarity	NPC263367
0.8992	High Similarity	NPC29799
0.8992	High Similarity	NPC10737
0.8992	High Similarity	NPC209985
0.8992	High Similarity	NPC471988
0.8992	High Similarity	NPC54743
0.8992	High Similarity	NPC477939
0.8992	High Similarity	NPC156502
0.8984	High Similarity	NPC244983
0.8984	High Similarity	NPC326095
0.8983	High Similarity	NPC81067
0.8983	High Similarity	NPC9341
0.8976	High Similarity	NPC227002
0.896	High Similarity	NPC245826
0.896	High Similarity	NPC252307
0.896	High Similarity	NPC474178
0.8952	High Similarity	NPC213552
0.8952	High Similarity	NPC120225
0.8952	High Similarity	NPC76451
0.8952	High Similarity	NPC178284
0.8952	High Similarity	NPC58607
0.8952	High Similarity	NPC304630
0.8952	High Similarity	NPC17837
0.8952	High Similarity	NPC191037
0.8943	High Similarity	NPC293701
0.8943	High Similarity	NPC48990
0.8943	High Similarity	NPC114901
0.8934	High Similarity	NPC30462
0.8923	High Similarity	NPC281780
0.8917	High Similarity	NPC474320
0.8915	High Similarity	NPC24490
0.8915	High Similarity	NPC141765
0.8915	High Similarity	NPC165155
0.8915	High Similarity	NPC34103
0.8898	High Similarity	NPC473264
0.8898	High Similarity	NPC474017
0.8898	High Similarity	NPC47194
0.8898	High Similarity	NPC475815
0.888	High Similarity	NPC292056
0.888	High Similarity	NPC21563
0.888	High Similarity	NPC41706
0.888	High Similarity	NPC118787
0.888	High Similarity	NPC163332
0.888	High Similarity	NPC147821
0.888	High Similarity	NPC183181
0.888	High Similarity	NPC319625
0.888	High Similarity	NPC111247
0.8879	High Similarity	NPC8547
0.8879	High Similarity	NPC257124
0.8879	High Similarity	NPC156840
0.8879	High Similarity	NPC173746
0.8871	High Similarity	NPC251855
0.8871	High Similarity	NPC17943
0.8871	High Similarity	NPC208950
0.8871	High Similarity	NPC475169
0.8871	High Similarity	NPC233410
0.8871	High Similarity	NPC53305
0.8871	High Similarity	NPC472093
0.8871	High Similarity	NPC221077
0.8871	High Similarity	NPC116907
0.8871	High Similarity	NPC298757
0.8871	High Similarity	NPC257589
0.8871	High Similarity	NPC117214
0.8871	High Similarity	NPC57490
0.8871	High Similarity	NPC193544
0.8871	High Similarity	NPC289459
0.8871	High Similarity	NPC203133
0.8862	High Similarity	NPC197757
0.8862	High Similarity	NPC228922
0.8862	High Similarity	NPC473451
0.8855	High Similarity	NPC193666
0.8855	High Similarity	NPC88640
0.8855	High Similarity	NPC123526
0.8852	High Similarity	NPC476343
0.8846	High Similarity	NPC90431
0.8843	High Similarity	NPC344161
0.8837	High Similarity	NPC478085
0.8819	High Similarity	NPC143483
0.881	High Similarity	NPC206615
0.881	High Similarity	NPC186843
0.881	High Similarity	NPC98631
0.881	High Similarity	NPC470213

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 NPC31344 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	275
0.1-0.2	864
0.2-0.3	1441
0.3-0.4	2658
0.4-0.5	1987
0.5-0.6	1064
0.6-0.7	698
0.7-0.8	151
0.8-0.85	8
0.85-0.9	4
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9052	High Similarity	NPD5283	Phase 1
0.8879	High Similarity	NPD228	Approved
0.874	High Similarity	NPD3027	Phase 3
0.8707	High Similarity	NPD3022	Approved
0.8707	High Similarity	NPD3021	Approved
0.856	High Similarity	NPD4379	Clinical (unspecified phase)
0.8538	High Similarity	NPD3619	Clinical (unspecified phase)
0.8538	High Similarity	NPD3620	Phase 2
0.8258	Intermediate Similarity	NPD4060	Phase 1
0.816	Intermediate Similarity	NPD1357	Approved
0.8151	Intermediate Similarity	NPD2684	Approved
0.813	Intermediate Similarity	NPD7157	Approved
0.8125	Intermediate Similarity	NPD3600	Clinical (unspecified phase)
0.812	Intermediate Similarity	NPD1613	Approved
0.812	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.811	Intermediate Similarity	NPD3705	Approved
0.8092	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.8033	Intermediate Similarity	NPD7843	Approved
0.8015	Intermediate Similarity	NPD2861	Phase 2
0.8015	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.8	Intermediate Similarity	NPD5536	Phase 2
0.7931	Intermediate Similarity	NPD3020	Approved
0.7857	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7857	Intermediate Similarity	NPD6331	Phase 2
0.7857	Intermediate Similarity	NPD4110	Phase 3
0.7852	Intermediate Similarity	NPD1558	Phase 1
0.7836	Intermediate Similarity	NPD5111	Phase 2
0.7836	Intermediate Similarity	NPD5109	Approved
0.7836	Intermediate Similarity	NPD5110	Phase 2
0.782	Intermediate Similarity	NPD4908	Phase 1
0.7803	Intermediate Similarity	NPD6584	Phase 3
0.7794	Intermediate Similarity	NPD6355	Discontinued
0.7778	Intermediate Similarity	NPD2674	Phase 3
0.7761	Intermediate Similarity	NPD7095	Approved
0.771	Intermediate Similarity	NPD2982	Phase 2
0.771	Intermediate Similarity	NPD2983	Phase 2
0.7704	Intermediate Similarity	NPD3144	Approved
0.7704	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7704	Intermediate Similarity	NPD3145	Approved
0.7698	Intermediate Similarity	NPD2161	Phase 2
0.7698	Intermediate Similarity	NPD6671	Approved
0.7692	Intermediate Similarity	NPD1610	Phase 2
0.7692	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7687	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7686	Intermediate Similarity	NPD968	Approved
0.7674	Intermediate Similarity	NPD6516	Phase 2
0.7674	Intermediate Similarity	NPD5846	Approved
0.7672	Intermediate Similarity	NPD2860	Approved
0.7672	Intermediate Similarity	NPD2859	Approved
0.7664	Intermediate Similarity	NPD3657	Discovery
0.7664	Intermediate Similarity	NPD5735	Approved
0.766	Intermediate Similarity	NPD4236	Phase 3
0.766	Intermediate Similarity	NPD4237	Approved
0.766	Intermediate Similarity	NPD3060	Approved
0.7634	Intermediate Similarity	NPD2981	Phase 2
0.7626	Intermediate Similarity	NPD6028	Clinical (unspecified phase)
0.7626	Intermediate Similarity	NPD6029	Clinical (unspecified phase)
0.7616	Intermediate Similarity	NPD6234	Discontinued
0.7612	Intermediate Similarity	NPD9494	Approved
0.7612	Intermediate Similarity	NPD3018	Phase 2
0.7586	Intermediate Similarity	NPD2934	Approved
0.7586	Intermediate Similarity	NPD9296	Approved
0.7586	Intermediate Similarity	NPD2933	Approved
0.7576	Intermediate Similarity	NPD6582	Phase 2
0.7576	Intermediate Similarity	NPD6583	Phase 3
0.7576	Intermediate Similarity	NPD5327	Phase 3
0.7554	Intermediate Similarity	NPD6895	Approved
0.7554	Intermediate Similarity	NPD6896	Approved
0.7538	Intermediate Similarity	NPD2667	Approved
0.7538	Intermediate Similarity	NPD2668	Approved
0.7537	Intermediate Similarity	NPD4624	Approved
0.7535	Intermediate Similarity	NPD4162	Approved
0.7518	Intermediate Similarity	NPD1726	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD5451	Approved
0.75	Intermediate Similarity	NPD2232	Approved
0.75	Intermediate Similarity	NPD2230	Approved
0.75	Intermediate Similarity	NPD2233	Approved
0.7483	Intermediate Similarity	NPD3882	Suspended
0.748	Intermediate Similarity	NPD290	Approved
0.7467	Intermediate Similarity	NPD2977	Approved
0.7467	Intermediate Similarity	NPD2978	Approved
0.7465	Intermediate Similarity	NPD7037	Approved
0.7464	Intermediate Similarity	NPD4140	Approved
0.7464	Intermediate Similarity	NPD5837	Clinical (unspecified phase)
0.746	Intermediate Similarity	NPD5535	Approved
0.7445	Intermediate Similarity	NPD6798	Discontinued
0.7431	Intermediate Similarity	NPD5241	Discontinued
0.7424	Intermediate Similarity	NPD3092	Approved
0.7413	Intermediate Similarity	NPD6674	Discontinued
0.7413	Intermediate Similarity	NPD5177	Phase 3
0.7405	Intermediate Similarity	NPD4626	Approved
0.74	Intermediate Similarity	NPD37	Approved
0.74	Intermediate Similarity	NPD1934	Approved
0.7397	Intermediate Similarity	NPD1754	Clinical (unspecified phase)
0.7394	Intermediate Similarity	NPD7266	Discontinued
0.7394	Intermediate Similarity	NPD2029	Clinical (unspecified phase)
0.7394	Intermediate Similarity	NPD1375	Discontinued
0.7394	Intermediate Similarity	NPD5762	Approved
0.7394	Intermediate Similarity	NPD5763	Approved
0.7388	Intermediate Similarity	NPD8651	Approved
0.7388	Intermediate Similarity	NPD1283	Approved
0.7388	Intermediate Similarity	NPD2922	Phase 1
0.7385	Intermediate Similarity	NPD1548	Phase 1
0.7385	Intermediate Similarity	NPD1182	Approved
0.7385	Intermediate Similarity	NPD3091	Approved
0.7376	Intermediate Similarity	NPD5588	Approved
0.7368	Intermediate Similarity	NPD2235	Phase 2
0.7368	Intermediate Similarity	NPD2231	Phase 2
0.7368	Intermediate Similarity	NPD4967	Phase 2
0.7368	Intermediate Similarity	NPD1840	Phase 2
0.7368	Intermediate Similarity	NPD4966	Approved
0.7368	Intermediate Similarity	NPD4965	Approved
0.7361	Intermediate Similarity	NPD6658	Clinical (unspecified phase)
0.7361	Intermediate Similarity	NPD8166	Discontinued
0.7357	Intermediate Similarity	NPD6353	Approved
0.7357	Intermediate Similarity	NPD6653	Approved
0.7355	Intermediate Similarity	NPD291	Approved
0.7351	Intermediate Similarity	NPD5563	Clinical (unspecified phase)
0.7348	Intermediate Similarity	NPD3847	Discontinued
0.7347	Intermediate Similarity	NPD5261	Clinical (unspecified phase)
0.7339	Intermediate Similarity	NPD1358	Approved
0.7333	Intermediate Similarity	NPD3094	Phase 2
0.7328	Intermediate Similarity	NPD5585	Approved
0.7328	Intermediate Similarity	NPD1651	Approved
0.7328	Intermediate Similarity	NPD5691	Approved
0.7323	Intermediate Similarity	NPD821	Approved
0.732	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.732	Intermediate Similarity	NPD7831	Phase 2
0.732	Intermediate Similarity	NPD7833	Phase 2
0.7319	Intermediate Similarity	NPD5718	Phase 2
0.7313	Intermediate Similarity	NPD4749	Approved
0.7313	Intermediate Similarity	NPD1669	Approved
0.731	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7305	Intermediate Similarity	NPD4537	Clinical (unspecified phase)
0.7305	Intermediate Similarity	NPD4538	Approved
0.7305	Intermediate Similarity	NPD4536	Approved
0.7292	Intermediate Similarity	NPD5698	Clinical (unspecified phase)
0.729	Intermediate Similarity	NPD7199	Phase 2
0.7288	Intermediate Similarity	NPD1432	Clinical (unspecified phase)
0.7279	Intermediate Similarity	NPD4123	Phase 3
0.7278	Intermediate Similarity	NPD7228	Approved
0.7267	Intermediate Similarity	NPD7028	Phase 2
0.7266	Intermediate Similarity	NPD4062	Phase 3
0.7266	Intermediate Similarity	NPD6233	Phase 2
0.7261	Intermediate Similarity	NPD27	Approved
0.7261	Intermediate Similarity	NPD2489	Approved
0.7258	Intermediate Similarity	NPD3134	Approved
0.7254	Intermediate Similarity	NPD4108	Discontinued
0.7246	Intermediate Similarity	NPD4625	Phase 3
0.7241	Intermediate Similarity	NPD4628	Phase 3
0.7239	Intermediate Similarity	NPD1608	Approved
0.7237	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7237	Intermediate Similarity	NPD2801	Approved
0.7234	Intermediate Similarity	NPD2157	Approved
0.7234	Intermediate Similarity	NPD4097	Suspended
0.7231	Intermediate Similarity	NPD3596	Phase 2
0.723	Intermediate Similarity	NPD7527	Clinical (unspecified phase)
0.723	Intermediate Similarity	NPD52	Approved
0.723	Intermediate Similarity	NPD7526	Approved
0.7226	Intermediate Similarity	NPD1712	Approved
0.7222	Intermediate Similarity	NPD5958	Discontinued
0.7222	Intermediate Similarity	NPD4664	Clinical (unspecified phase)
0.7218	Intermediate Similarity	NPD3496	Discontinued
0.7214	Intermediate Similarity	NPD2979	Phase 3
0.7214	Intermediate Similarity	NPD2238	Phase 2
0.7203	Intermediate Similarity	NPD2438	Suspended
0.7197	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7194	Intermediate Similarity	NPD6410	Clinical (unspecified phase)
0.7192	Intermediate Similarity	NPD5084	Clinical (unspecified phase)
0.7185	Intermediate Similarity	NPD3685	Discontinued
0.7167	Intermediate Similarity	NPD288	Approved
0.7164	Intermediate Similarity	NPD1281	Approved
0.7154	Intermediate Similarity	NPD709	Approved
0.7153	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD6783	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD5058	Phase 3
0.7143	Intermediate Similarity	NPD7124	Phase 2
0.7143	Intermediate Similarity	NPD3095	Discontinued
0.7133	Intermediate Similarity	NPD5960	Phase 3
0.7132	Intermediate Similarity	NPD6696	Suspended
0.7122	Intermediate Similarity	NPD2669	Clinical (unspecified phase)
0.7121	Intermediate Similarity	NPD6580	Approved
0.7121	Intermediate Similarity	NPD1894	Discontinued
0.7121	Intermediate Similarity	NPD6581	Approved
0.7103	Intermediate Similarity	NPD2808	Discontinued
0.7103	Intermediate Similarity	NPD4534	Discontinued
0.7103	Intermediate Similarity	NPD7153	Discontinued
0.7101	Intermediate Similarity	NPD5736	Approved
0.7095	Intermediate Similarity	NPD4357	Discontinued
0.7095	Intermediate Similarity	NPD7041	Phase 2
0.7095	Intermediate Similarity	NPD7040	Clinical (unspecified phase)
0.7089	Intermediate Similarity	NPD2970	Approved
0.7089	Intermediate Similarity	NPD2969	Approved
0.7086	Intermediate Similarity	NPD4005	Discontinued
0.7086	Intermediate Similarity	NPD3866	Clinical (unspecified phase)
0.7083	Intermediate Similarity	NPD2935	Discontinued
0.7083	Intermediate Similarity	NPD844	Approved
0.7083	Intermediate Similarity	NPD6032	Approved
0.708	Intermediate Similarity	NPD3053	Approved
0.708	Intermediate Similarity	NPD3055	Approved

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