NPASS Compound

Structure

CID43158 OpenBabel06191715372D 38 40 0 0 1 0 0 0 0 0999 V2000 -2.3801 -3.1554 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 4.5000 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 -2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 2.5000 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 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 3 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 -1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.7071 -2.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 4.3301 4.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 4.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 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 -0.0000 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4483 -3.6730 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9239 -2.3827 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6730 -2.4483 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 36 1 0 0 0 0 2 6 2 0 0 0 0 2 14 1 0 0 0 0 3 7 2 0 0 0 0 3 15 1 0 0 0 0 4 8 2 0 0 0 0 4 14 1 0 0 0 0 5 9 2 0 0 0 0 5 15 1 0 0 0 0 6 16 1 0 0 0 0 7 17 1 0 0 0 0 8 22 1 0 0 0 0 9 23 1 0 0 0 0 10 14 2 0 0 0 0 10 18 1 0 0 0 0 11 15 2 0 0 0 0 11 19 1 0 0 0 0 12 20 1 0 0 0 0 12 26 1 0 0 0 0 13 21 1 0 0 0 0 13 26 1 0 0 0 0 16 18 2 0 0 0 0 16 27 1 0 0 0 0 17 19 2 0 0 0 0 17 28 1 0 0 0 0 18 29 1 0 0 0 0 19 30 1 0 0 0 0 20 24 1 0 0 0 0 20 37 1 0 0 0 0 21 24 1 0 0 0 0 21 38 1 0 0 0 0 22 31 2 0 0 0 0 22 37 1 0 0 0 0 23 32 2 0 0 0 0 23 38 1 0 0 0 0 24 33 1 0 0 0 0 25 26 1 0 0 0 0 25 34 2 0 0 0 0 25 36 1 0 0 0 0 26 35 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	530.14
Volume:	509.064
LogP:	2.069
LogD:	1.72
LogS:	-2.406
# Rotatable Bonds:	10
TPSA:	200.28
# H-Bond Aceptor:	12
# H-Bond Donor:	6
# Rings:	3
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.129
Synthetic Accessibility Score:	3.86
Fsp3:	0.269
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	1
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.015
MDCK Permeability:	1.4258151168178301e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.419
Human Intestinal Absorption (HIA):	0.95
20% Bioavailability (F20%):	0.997
30% Bioavailability (F30%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.21
Plasma Protein Binding (PPB):	97.27869415283203%
Volume Distribution (VD):	0.386
Pgp-substrate:	2.1588337421417236%

ADMET: Metabolism

CYP1A2-inhibitor:	0.066
CYP1A2-substrate:	0.072
CYP2C19-inhibitor:	0.268
CYP2C19-substrate:	0.057
CYP2C9-inhibitor:	0.496
CYP2C9-substrate:	0.897
CYP2D6-inhibitor:	0.419
CYP2D6-substrate:	0.242
CYP3A4-inhibitor:	0.13
CYP3A4-substrate:	0.16

ADMET: Excretion

Clearance (CL):	11.098
Half-life (T1/2):	0.932

ADMET: Toxicity

hERG Blockers:	0.088
Human Hepatotoxicity (H-HT):	0.286
Drug-inuced Liver Injury (DILI):	0.075
AMES Toxicity:	0.124
Rat Oral Acute Toxicity:	0.139
Maximum Recommended Daily Dose:	0.827
Skin Sensitization:	0.928
Carcinogencity:	0.231
Eye Corrosion:	0.003
Eye Irritation:	0.029
Respiratory Toxicity:	0.034

Download Data

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

Natural Product: NPC43158

Natural Product ID:	NPC43158
*Common Name:**	Macrathoin F
IUPAC Name:	methyl 3,5-bis[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]-1,4-dihydroxycyclohexane-1-carboxylate
Synonyms:	Macrathoin F
Standard InCHIKey:	VEBNYMXKXIIGFX-KBXRYBNXSA-N
Standard InCHI:	InChI=1S/C26H26O12/c1-36-25(34)26(35)12-20(37-22(31)8-4-14-2-6-16(27)18(29)10-14)24(33)21(13-26)38-23(32)9-5-15-3-7-17(28)19(30)11-15/h2-11,20-21,24,27-30,33,35H,12-13H2,1H3/b8-4+,9-5+
SMILES:	COC(=O)C1(O)CC(OC(=O)/C=C/c2ccc(c(c2)O)O)C(C(C1)OC(=O)/C=C/c1ccc(c(c1)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2048502
PubChem CID:	5319161
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000129] Alcohols and polyols [CHEMONTID:0001292] Cyclic alcohols and derivatives [CHEMONTID:0002509] Cyclitols and derivatives [CHEMONTID:0002512] Quinic acids and derivatives

*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
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	Flowers	n.a.	n.a.	DOI[10.1002/elan.200403102]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	flower	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	Flowers	n.a.	n.a.	DOI[10.1016/j.foodchem.2012.02.124]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	Flowers	n.a.	n.a.	PMID[11077184]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	Flowers	n.a.	n.a.	PMID[17328234]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	Flower buds	n.a.	n.a.	PMID[18321056]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	n.a.	flower	n.a.	PMID[21804227]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	n.a.	flower bud	n.a.	PMID[21942812]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	flower buds	Henan province, China	2005-MAY	PMID[21942812]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[23265495]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	Flower buds	n.a.	n.a.	PMID[24279769]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[6387056]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10506	Artemisia apiacea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1515	Lonicera japonica	Species	Caprifoliaceae	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	6
Others	6

Activity Type	# Activity
Individual Protein	12

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT568	Individual Protein	Matrix metalloproteinase-2	Homo sapiens	IC50	=	3880.0	nM	PMID[522560]
NPT567	Individual Protein	Matrix metalloproteinase 3	Homo sapiens	IC50	=	10360.0	nM	PMID[522560]
NPT280	Individual Protein	Matrix metalloproteinase 9	Homo sapiens	IC50	=	11610.0	nM	PMID[522560]
NPT1089	Individual Protein	Matrix metalloproteinase 12	Homo sapiens	IC50	=	1200.0	nM	PMID[522560]
NPT1090	Individual Protein	Matrix metalloproteinase 13	Homo sapiens	IC50	=	7620.0	nM	PMID[522560]
NPT568	Individual Protein	Matrix metalloproteinase-2	Homo sapiens	Inhibition	>	30.0	%	PMID[522560]
NPT567	Individual Protein	Matrix metalloproteinase 3	Homo sapiens	Inhibition	>	30.0	%	PMID[522560]
NPT280	Individual Protein	Matrix metalloproteinase 9	Homo sapiens	Inhibition	>	30.0	%	PMID[522560]
NPT1089	Individual Protein	Matrix metalloproteinase 12	Homo sapiens	Inhibition	>	30.0	%	PMID[522560]
NPT1090	Individual Protein	Matrix metalloproteinase 13	Homo sapiens	Inhibition	>	30.0	%	PMID[522560]
NPT69	Individual Protein	Matrix metalloproteinase-1	Homo sapiens	IC50	=	16320.0	nM	PMID[522560]
NPT69	Individual Protein	Matrix metalloproteinase-1	Homo sapiens	Inhibition	>	30.0	%	PMID[522560]

☑ 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 NPC43158 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	306
0.1-0.2	1241
0.2-0.3	3058
0.3-0.4	6918
0.4-0.5	10409
0.5-0.6	5943
0.6-0.7	8142
0.7-0.8	6201
0.8-0.85	352
0.85-0.9	60
0.9-0.95	23
0.95-1	44

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC472016
1.0	High Similarity	NPC258469
1.0	High Similarity	NPC192831
1.0	High Similarity	NPC277315
0.9926	High Similarity	NPC477335
0.9926	High Similarity	NPC206095
0.9926	High Similarity	NPC224389
0.9926	High Similarity	NPC297517
0.9926	High Similarity	NPC35702
0.9926	High Similarity	NPC471027
0.9926	High Similarity	NPC13818
0.9853	High Similarity	NPC284948
0.9853	High Similarity	NPC37331
0.9853	High Similarity	NPC319628
0.9853	High Similarity	NPC220664
0.9853	High Similarity	NPC303090
0.9778	High Similarity	NPC274891
0.9778	High Similarity	NPC303683
0.9778	High Similarity	NPC476819
0.9778	High Similarity	NPC295492
0.9778	High Similarity	NPC476820
0.9778	High Similarity	NPC26241
0.9778	High Similarity	NPC205751
0.9778	High Similarity	NPC474875
0.9704	High Similarity	NPC219428
0.9704	High Similarity	NPC152942
0.9704	High Similarity	NPC37250
0.9704	High Similarity	NPC302857
0.9704	High Similarity	NPC278068
0.9704	High Similarity	NPC142703
0.9643	High Similarity	NPC471076
0.9643	High Similarity	NPC192568
0.9571	High Similarity	NPC322660
0.9568	High Similarity	NPC477333
0.9559	High Similarity	NPC283560
0.9559	High Similarity	NPC24295
0.9507	High Similarity	NPC306343
0.9481	High Similarity	NPC233350
0.9481	High Similarity	NPC182217
0.9481	High Similarity	NPC70680
0.9437	High Similarity	NPC42464
0.9407	High Similarity	NPC68517
0.9375	High Similarity	NPC163883
0.9375	High Similarity	NPC93498
0.9366	High Similarity	NPC43123
0.9362	High Similarity	NPC98356
0.931	High Similarity	NPC19380
0.931	High Similarity	NPC146277
0.9184	High Similarity	NPC145425
0.9172	High Similarity	NPC477334
0.9122	High Similarity	NPC470896
0.9122	High Similarity	NPC473275
0.9085	High Similarity	NPC50221
0.9085	High Similarity	NPC114242
0.9051	High Similarity	NPC155209
0.9051	High Similarity	NPC168799
0.9041	High Similarity	NPC252979
0.8978	High Similarity	NPC18074
0.8978	High Similarity	NPC61
0.8978	High Similarity	NPC25581
0.8978	High Similarity	NPC5419
0.8951	High Similarity	NPC226738
0.8951	High Similarity	NPC22176
0.8951	High Similarity	NPC190587
0.8951	High Similarity	NPC121573
0.8936	High Similarity	NPC179505
0.8936	High Similarity	NPC156709
0.8905	High Similarity	NPC198388
0.8897	High Similarity	NPC229264
0.8849	High Similarity	NPC474895
0.8849	High Similarity	NPC106406
0.8836	High Similarity	NPC142528
0.8811	High Similarity	NPC477277
0.8811	High Similarity	NPC477278
0.8794	High Similarity	NPC67349
0.8794	High Similarity	NPC279676
0.8792	High Similarity	NPC44730
0.8742	High Similarity	NPC134925
0.8741	High Similarity	NPC38473
0.8741	High Similarity	NPC477279
0.8707	High Similarity	NPC472969
0.8707	High Similarity	NPC120621
0.8707	High Similarity	NPC248257
0.8675	High Similarity	NPC203757
0.8671	High Similarity	NPC75763
0.8671	High Similarity	NPC225036
0.8671	High Similarity	NPC288452
0.8671	High Similarity	NPC12218
0.8671	High Similarity	NPC289690
0.8671	High Similarity	NPC105525
0.8658	High Similarity	NPC140151
0.8654	High Similarity	NPC471823
0.8649	High Similarity	NPC476394
0.8649	High Similarity	NPC98809
0.8649	High Similarity	NPC75945
0.8649	High Similarity	NPC92117
0.8645	High Similarity	NPC227297
0.8643	High Similarity	NPC471749
0.8639	High Similarity	NPC283081
0.8639	High Similarity	NPC299090
0.8639	High Similarity	NPC221383
0.8639	High Similarity	NPC143892
0.8633	High Similarity	NPC318799
0.8601	High Similarity	NPC239943
0.86	High Similarity	NPC246566
0.86	High Similarity	NPC106818
0.86	High Similarity	NPC75695
0.86	High Similarity	NPC95498
0.8591	High Similarity	NPC32197
0.8571	High Similarity	NPC473867
0.8562	High Similarity	NPC474692
0.8562	High Similarity	NPC160378
0.8561	High Similarity	NPC32626
0.8561	High Similarity	NPC217052
0.8561	High Similarity	NPC329344
0.8561	High Similarity	NPC237506
0.8543	High Similarity	NPC16024
0.8543	High Similarity	NPC61152
0.8543	High Similarity	NPC205037
0.8543	High Similarity	NPC3746
0.8543	High Similarity	NPC87403
0.8543	High Similarity	NPC44260
0.854	High Similarity	NPC475695
0.8533	High Similarity	NPC300329
0.8533	High Similarity	NPC243891
0.8531	High Similarity	NPC84789
0.8531	High Similarity	NPC302583
0.8531	High Similarity	NPC100558
0.8531	High Similarity	NPC310252
0.8521	High Similarity	NPC18646
0.8503	High Similarity	NPC53884
0.8503	High Similarity	NPC258671
0.8489	Intermediate Similarity	NPC226855
0.8489	Intermediate Similarity	NPC94810
0.8487	Intermediate Similarity	NPC191046
0.8487	Intermediate Similarity	NPC327032
0.8487	Intermediate Similarity	NPC194095
0.8483	Intermediate Similarity	NPC9218
0.8481	Intermediate Similarity	NPC128403
0.8477	Intermediate Similarity	NPC476434
0.8477	Intermediate Similarity	NPC267091
0.8467	Intermediate Similarity	NPC259576
0.8467	Intermediate Similarity	NPC473091
0.8467	Intermediate Similarity	NPC221091
0.8462	Intermediate Similarity	NPC156892
0.8456	Intermediate Similarity	NPC98009
0.8451	Intermediate Similarity	NPC886
0.8451	Intermediate Similarity	NPC34293
0.8451	Intermediate Similarity	NPC248150
0.8451	Intermediate Similarity	NPC135127
0.8451	Intermediate Similarity	NPC287597
0.8442	Intermediate Similarity	NPC133984
0.8442	Intermediate Similarity	NPC226759
0.8442	Intermediate Similarity	NPC472860
0.8435	Intermediate Similarity	NPC304956
0.8435	Intermediate Similarity	NPC229036
0.8435	Intermediate Similarity	NPC473090
0.8435	Intermediate Similarity	NPC183824
0.8435	Intermediate Similarity	NPC470130
0.8406	Intermediate Similarity	NPC118584
0.84	Intermediate Similarity	NPC478242
0.8397	Intermediate Similarity	NPC311803
0.8397	Intermediate Similarity	NPC472859
0.8397	Intermediate Similarity	NPC25389
0.8394	Intermediate Similarity	NPC85565
0.8392	Intermediate Similarity	NPC123988
0.8387	Intermediate Similarity	NPC289811
0.8387	Intermediate Similarity	NPC160780
0.8387	Intermediate Similarity	NPC74319
0.8387	Intermediate Similarity	NPC287872
0.838	Intermediate Similarity	NPC156124
0.838	Intermediate Similarity	NPC1321
0.838	Intermediate Similarity	NPC304929
0.8378	Intermediate Similarity	NPC108455
0.8377	Intermediate Similarity	NPC247629
0.8377	Intermediate Similarity	NPC471405
0.8377	Intermediate Similarity	NPC239019
0.8369	Intermediate Similarity	NPC108553
0.8367	Intermediate Similarity	NPC285550
0.8366	Intermediate Similarity	NPC477299
0.8366	Intermediate Similarity	NPC125487
0.8366	Intermediate Similarity	NPC469888
0.8366	Intermediate Similarity	NPC281703
0.8356	Intermediate Similarity	NPC326065
0.8355	Intermediate Similarity	NPC134905
0.8355	Intermediate Similarity	NPC36130
0.8345	Intermediate Similarity	NPC89105
0.8345	Intermediate Similarity	NPC328273
0.8345	Intermediate Similarity	NPC64141
0.8345	Intermediate Similarity	NPC321184
0.8345	Intermediate Similarity	NPC68092
0.8345	Intermediate Similarity	NPC476383
0.8345	Intermediate Similarity	NPC321638
0.8345	Intermediate Similarity	NPC171134
0.8345	Intermediate Similarity	NPC220942
0.8345	Intermediate Similarity	NPC158654
0.8345	Intermediate Similarity	NPC472350
0.8345	Intermediate Similarity	NPC81515
0.8345	Intermediate Similarity	NPC284409
0.8345	Intermediate Similarity	NPC197316

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 NPC43158 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	258
0.1-0.2	761
0.2-0.3	1654
0.3-0.4	2712
0.4-0.5	2071
0.5-0.6	1093
0.6-0.7	510
0.7-0.8	87
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9853	High Similarity	NPD6190	Approved
0.838	Intermediate Similarity	NPD230	Phase 1
0.8345	Intermediate Similarity	NPD7266	Discontinued
0.8258	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.8072	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7988	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7901	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7901	Intermediate Similarity	NPD6166	Phase 2
0.7901	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7892	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7848	Intermediate Similarity	NPD3817	Phase 2
0.7831	Intermediate Similarity	NPD7685	Pre-registration
0.7799	Intermediate Similarity	NPD3882	Suspended
0.7785	Intermediate Similarity	NPD2801	Approved
0.7778	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.774	Intermediate Similarity	NPD6233	Phase 2
0.773	Intermediate Similarity	NPD9269	Phase 2
0.7722	Intermediate Similarity	NPD1934	Approved
0.7702	Intermediate Similarity	NPD6234	Discontinued
0.7697	Intermediate Similarity	NPD8166	Discontinued
0.7697	Intermediate Similarity	NPD3818	Discontinued
0.7697	Intermediate Similarity	NPD4628	Phase 3
0.7673	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7665	Intermediate Similarity	NPD6797	Phase 2
0.7651	Intermediate Similarity	NPD5844	Phase 1
0.764	Intermediate Similarity	NPD7075	Discontinued
0.7626	Intermediate Similarity	NPD9545	Approved
0.7625	Intermediate Similarity	NPD5402	Approved
0.7619	Intermediate Similarity	NPD7251	Discontinued
0.761	Intermediate Similarity	NPD37	Approved
0.7603	Intermediate Similarity	NPD3027	Phase 3
0.758	Intermediate Similarity	NPD1653	Approved
0.7578	Intermediate Similarity	NPD4966	Approved
0.7578	Intermediate Similarity	NPD4967	Phase 2
0.7578	Intermediate Similarity	NPD4965	Approved
0.7564	Intermediate Similarity	NPD1512	Approved
0.7561	Intermediate Similarity	NPD6232	Discontinued
0.7552	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7551	Intermediate Similarity	NPD3764	Approved
0.7545	Intermediate Similarity	NPD7054	Approved
0.7516	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD8150	Discontinued
0.75	Intermediate Similarity	NPD6801	Discontinued
0.75	Intermediate Similarity	NPD7074	Phase 3
0.75	Intermediate Similarity	NPD7472	Approved
0.7485	Intermediate Similarity	NPD3751	Discontinued
0.7485	Intermediate Similarity	NPD7228	Approved
0.7484	Intermediate Similarity	NPD4380	Phase 2
0.7471	Intermediate Similarity	NPD7808	Phase 3
0.7466	Intermediate Similarity	NPD9494	Approved
0.7453	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7453	Intermediate Similarity	NPD1465	Phase 2
0.745	Intermediate Similarity	NPD943	Approved
0.7447	Intermediate Similarity	NPD9268	Approved
0.7436	Intermediate Similarity	NPD1511	Approved
0.7436	Intermediate Similarity	NPD6799	Approved
0.7432	Intermediate Similarity	NPD6798	Discontinued
0.7429	Intermediate Similarity	NPD7879	Clinical (unspecified phase)
0.7425	Intermediate Similarity	NPD7473	Discontinued
0.7421	Intermediate Similarity	NPD3455	Phase 2
0.741	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7394	Intermediate Similarity	NPD7199	Phase 2
0.7349	Intermediate Similarity	NPD3787	Discontinued
0.7333	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7333	Intermediate Similarity	NPD1613	Approved
0.7317	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.7315	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7314	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7299	Intermediate Similarity	NPD8434	Phase 2
0.7296	Intermediate Similarity	NPD5403	Approved
0.729	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7255	Intermediate Similarity	NPD651	Clinical (unspecified phase)
0.7248	Intermediate Similarity	NPD7095	Approved
0.7222	Intermediate Similarity	NPD6385	Approved
0.7222	Intermediate Similarity	NPD6386	Approved
0.7208	Intermediate Similarity	NPD2935	Discontinued
0.7186	Intermediate Similarity	NPD8127	Discontinued
0.7171	Intermediate Similarity	NPD6355	Discontinued
0.717	Intermediate Similarity	NPD5401	Approved
0.717	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.716	Intermediate Similarity	NPD6599	Discontinued
0.7152	Intermediate Similarity	NPD4062	Phase 3
0.7143	Intermediate Similarity	NPD7033	Discontinued
0.7135	Intermediate Similarity	NPD7804	Clinical (unspecified phase)
0.7134	Intermediate Similarity	NPD7819	Suspended
0.7126	Intermediate Similarity	NPD5494	Approved
0.7117	Intermediate Similarity	NPD7411	Suspended
0.7105	Intermediate Similarity	NPD7966	Clinical (unspecified phase)
0.7091	Intermediate Similarity	NPD5353	Approved
0.7067	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7063	Intermediate Similarity	NPD5536	Phase 2
0.7063	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7063	Intermediate Similarity	NPD7422	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD447	Suspended
0.7056	Intermediate Similarity	NPD6535	Approved
0.7056	Intermediate Similarity	NPD6534	Approved
0.7032	Intermediate Similarity	NPD1510	Phase 2
0.7027	Intermediate Similarity	NPD7435	Discontinued
0.7011	Intermediate Similarity	NPD6559	Discontinued
0.7011	Intermediate Similarity	NPD7038	Approved
0.7011	Intermediate Similarity	NPD7039	Approved
0.7011	Intermediate Similarity	NPD7240	Approved
0.7007	Intermediate Similarity	NPD1608	Approved
0.7006	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7006	Intermediate Similarity	NPD1549	Phase 2
0.7	Intermediate Similarity	NPD5242	Approved
0.7	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.6993	Remote Similarity	NPD825	Approved
0.6993	Remote Similarity	NPD4060	Phase 1
0.6993	Remote Similarity	NPD826	Approved
0.6987	Remote Similarity	NPD9570	Approved
0.6978	Remote Similarity	NPD3021	Approved
0.6978	Remote Similarity	NPD3022	Approved
0.6972	Remote Similarity	NPD2629	Approved
0.6957	Remote Similarity	NPD6782	Approved
0.6957	Remote Similarity	NPD6780	Approved
0.6957	Remote Similarity	NPD6777	Approved
0.6957	Remote Similarity	NPD6776	Approved
0.6957	Remote Similarity	NPD6781	Approved
0.6957	Remote Similarity	NPD9265	Clinical (unspecified phase)
0.6957	Remote Similarity	NPD6778	Approved
0.6957	Remote Similarity	NPD7410	Clinical (unspecified phase)
0.6957	Remote Similarity	NPD6779	Approved
0.6948	Remote Similarity	NPD4340	Discontinued
0.6943	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.6943	Remote Similarity	NPD1550	Clinical (unspecified phase)
0.694	Remote Similarity	NPD7699	Phase 2
0.694	Remote Similarity	NPD7700	Phase 2
0.6928	Remote Similarity	NPD8455	Phase 2
0.6928	Remote Similarity	NPD6663	Approved
0.6918	Remote Similarity	NPD3750	Approved
0.6918	Remote Similarity	NPD4110	Phase 3
0.6918	Remote Similarity	NPD4109	Clinical (unspecified phase)
0.6918	Remote Similarity	NPD6398	Clinical (unspecified phase)
0.6898	Remote Similarity	NPD8320	Phase 1
0.6898	Remote Similarity	NPD8319	Approved
0.6894	Remote Similarity	NPD4357	Discontinued
0.689	Remote Similarity	NPD3226	Approved
0.6887	Remote Similarity	NPD5736	Approved
0.6886	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6883	Remote Similarity	NPD1240	Approved
0.6879	Remote Similarity	NPD2796	Approved
0.6879	Remote Similarity	NPD1551	Phase 2
0.6875	Remote Similarity	NPD3887	Approved
0.6875	Remote Similarity	NPD2354	Approved
0.6864	Remote Similarity	NPD919	Approved
0.686	Remote Similarity	NPD7852	Clinical (unspecified phase)
0.6859	Remote Similarity	NPD7097	Phase 1
0.6852	Remote Similarity	NPD2533	Approved
0.6852	Remote Similarity	NPD3688	Clinical (unspecified phase)
0.6852	Remote Similarity	NPD3146	Approved
0.6852	Remote Similarity	NPD2532	Approved
0.6852	Remote Similarity	NPD2534	Approved
0.6845	Remote Similarity	NPD7768	Phase 2
0.6839	Remote Similarity	NPD555	Phase 2
0.6836	Remote Similarity	NPD8312	Approved
0.6836	Remote Similarity	NPD8313	Approved
0.6824	Remote Similarity	NPD1535	Discovery
0.6815	Remote Similarity	NPD1509	Clinical (unspecified phase)
0.6813	Remote Similarity	NPD1878	Clinical (unspecified phase)
0.681	Remote Similarity	NPD6273	Approved
0.6806	Remote Similarity	NPD7874	Approved
0.6806	Remote Similarity	NPD4198	Discontinued
0.6806	Remote Similarity	NPD7875	Clinical (unspecified phase)
0.6805	Remote Similarity	NPD3749	Approved
0.6803	Remote Similarity	NPD17	Approved
0.6802	Remote Similarity	NPD3926	Phase 2
0.68	Remote Similarity	NPD3225	Approved
0.6798	Remote Similarity	NPD7090	Clinical (unspecified phase)
0.6795	Remote Similarity	NPD6653	Approved
0.6795	Remote Similarity	NPD1607	Approved
0.6792	Remote Similarity	NPD4534	Discontinued
0.6788	Remote Similarity	NPD7458	Discontinued
0.6784	Remote Similarity	NPD1247	Approved
0.6784	Remote Similarity	NPD6959	Discontinued
0.6779	Remote Similarity	NPD1481	Phase 2
0.6772	Remote Similarity	NPD5408	Approved
0.6772	Remote Similarity	NPD2438	Suspended
0.6772	Remote Similarity	NPD5406	Approved
0.6772	Remote Similarity	NPD5404	Approved
0.6772	Remote Similarity	NPD5405	Approved
0.6761	Remote Similarity	NPD228	Approved
0.6759	Remote Similarity	NPD9493	Approved
0.6755	Remote Similarity	NPD2797	Approved
0.6755	Remote Similarity	NPD7697	Approved
0.6755	Remote Similarity	NPD7698	Approved
0.6755	Remote Similarity	NPD7696	Phase 3
0.6753	Remote Similarity	NPD3268	Approved
0.675	Remote Similarity	NPD1652	Phase 2
0.6744	Remote Similarity	NPD7229	Phase 3
0.674	Remote Similarity	NPD8361	Approved
0.674	Remote Similarity	NPD8360	Approved
0.6738	Remote Similarity	NPD2067	Discontinued
0.6733	Remote Similarity	NPD2983	Phase 2
0.6733	Remote Similarity	NPD2982	Phase 2
0.6731	Remote Similarity	NPD1933	Approved
0.673	Remote Similarity	NPD2029	Clinical (unspecified phase)
0.6728	Remote Similarity	NPD7236	Approved
0.6723	Remote Similarity	NPD8368	Discontinued
0.672	Remote Similarity	NPD7237	Clinical (unspecified phase)

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