NPASS Compound

Structure

NPC82056 OpenBabel07101718202D 47 52 0 0 1 0 0 0 0 0999 V2000 -7.7942 -1.5000 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 -10.3923 1.0000 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 -2.5981 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3923 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 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 -6.0622 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -3.0000 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 -7.7942 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3923 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -0.5000 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 -4.3301 -3.5000 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 -12.1244 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -0.5000 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 -5.1962 -3.0000 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 -9.5263 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.5263 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 0.0000 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 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -1.5000 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 -6.9282 -2.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -12.1244 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 -2.0000 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 -9.5263 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 38 1 0 0 0 0 2 39 1 0 0 0 0 3 44 1 0 0 0 0 4 45 1 0 0 0 0 5 46 1 0 0 0 0 6 8 2 0 0 0 0 6 22 1 0 0 0 0 7 9 2 0 0 0 0 7 21 1 0 0 0 0 8 29 1 0 0 0 0 9 30 1 0 0 0 0 10 13 1 0 0 0 0 10 23 1 0 0 0 0 11 12 1 0 0 0 0 11 24 1 0 0 0 0 12 38 1 0 0 0 0 13 39 1 0 0 0 0 14 21 2 0 0 0 0 14 27 1 0 0 0 0 15 22 2 0 0 0 0 15 26 1 0 0 0 0 16 21 1 0 0 0 0 17 23 2 0 0 0 0 17 31 1 0 0 0 0 18 24 2 0 0 0 0 18 33 1 0 0 0 0 19 25 2 0 0 0 0 19 32 1 0 0 0 0 20 22 1 0 0 0 0 20 40 2 0 0 0 0 23 25 1 0 0 0 0 24 34 1 0 0 0 0 25 37 1 0 0 0 0 26 27 1 0 0 0 0 26 29 2 0 0 0 0 27 30 2 0 0 0 0 28 16 1 1 0 0 0 28 34 1 0 0 0 0 28 38 1 0 0 0 0 29 41 1 0 0 0 0 30 44 1 0 0 0 0 31 32 2 0 0 0 0 31 45 1 0 0 0 0 32 47 1 0 0 0 0 33 35 2 0 0 0 0 33 46 1 0 0 0 0 34 36 2 0 0 0 0 35 36 1 0 0 0 0 35 42 1 0 0 0 0 36 47 1 0 0 0 0 37 39 1 0 0 0 0 37 43 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	638.26
Volume:	652.574
LogP:	4.955
LogD:	3.213
LogS:	-4.461
# Rotatable Bonds:	9
TPSA:	118.0
# H-Bond Aceptor:	10
# H-Bond Donor:	2
# Rings:	6
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.22
Synthetic Accessibility Score:	3.664
Fsp3:	0.297
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.201
MDCK Permeability:	1.6219615645240992e-05
Pgp-inhibitor:	0.724
Pgp-substrate:	0.555
Human Intestinal Absorption (HIA):	0.068
20% Bioavailability (F20%):	0.017
30% Bioavailability (F30%):	0.745

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.077
Plasma Protein Binding (PPB):	86.7734603881836%
Volume Distribution (VD):	1.245
Pgp-substrate:	8.700346946716309%

ADMET: Metabolism

CYP1A2-inhibitor:	0.095
CYP1A2-substrate:	0.957
CYP2C19-inhibitor:	0.134
CYP2C19-substrate:	0.747
CYP2C9-inhibitor:	0.208
CYP2C9-substrate:	0.679
CYP2D6-inhibitor:	0.013
CYP2D6-substrate:	0.919
CYP3A4-inhibitor:	0.327
CYP3A4-substrate:	0.926

ADMET: Excretion

Clearance (CL):	5.41
Half-life (T1/2):	0.465

ADMET: Toxicity

hERG Blockers:	0.733
Human Hepatotoxicity (H-HT):	0.105
Drug-inuced Liver Injury (DILI):	0.509
AMES Toxicity:	0.267
Rat Oral Acute Toxicity:	0.357
Maximum Recommended Daily Dose:	0.968
Skin Sensitization:	0.188
Carcinogencity:	0.057
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.866

Download Data

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

Natural Product: NPC82056

Natural Product ID:	NPC82056
*Common Name:**	Secantioquine
IUPAC Name:	4-hydroxy-3-[5-[[(1S)-7-hydroxy-6-methoxy-8-[(6-methoxy-2-methyl-1-oxo-3,4-dihydroisoquinolin-7-yl)oxy]-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]methyl]-2-methoxyphenyl]benzaldehyde
Synonyms:	Secantioquine
Standard InCHIKey:	ZOBAYWQPWZMJPP-NDEPHWFRSA-N
Standard InCHI:	InChI=1S/C37H38N2O8/c1-38-12-11-24-18-33(46-5)35(42)36(47-32-19-25-23(17-31(32)45-4)10-13-39(2)37(25)43)34(24)28(38)16-21-7-9-30(44-3)27(14-21)26-15-22(20-40)6-8-29(26)41/h6-9,14-15,17-20,28,41-42H,10-13,16H2,1-5H3/t28-/m0/s1
SMILES:	O=Cc1ccc(c(c1)c1cc(ccc1OC)C[C@@H]1N(C)CCc2c1c(Oc1cc3c(cc1OC)CCN(C3=O)C)c(c(c2)OC)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL450155
PubChem CID:	44559885
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0000054] Benzylisoquinolines

*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
NPO33281	pseuhxandra sclerocarpa	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[8676127]

☑ 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	1

Activity Type	# Activity
Individual Protein	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1073	Individual Protein	Dopamine transporter	Rattus norvegicus	IC50	>	100000.0	nM	PMID[555502]
NPT2	Others	Unspecified		Ratio IC50	<	0.1	n.a.	PMID[555502]

☑ 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 NPC82056 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	352
0.1-0.2	1660
0.2-0.3	5978
0.3-0.4	11485
0.4-0.5	4906
0.5-0.6	7235
0.6-0.7	8782
0.7-0.8	2216
0.8-0.85	72
0.85-0.9	9
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9794	High Similarity	NPC38964
0.8705	High Similarity	NPC275680
0.8705	High Similarity	NPC22115
0.8601	High Similarity	NPC16357
0.8601	High Similarity	NPC95426
0.8601	High Similarity	NPC302245
0.8564	High Similarity	NPC206900
0.8557	High Similarity	NPC65312
0.8557	High Similarity	NPC139783
0.85	High Similarity	NPC475654
0.8497	Intermediate Similarity	NPC30779
0.8497	Intermediate Similarity	NPC185639
0.8497	Intermediate Similarity	NPC279228
0.8497	Intermediate Similarity	NPC8836
0.8497	Intermediate Similarity	NPC42663
0.8497	Intermediate Similarity	NPC222661
0.8497	Intermediate Similarity	NPC328155
0.8497	Intermediate Similarity	NPC7715
0.8497	Intermediate Similarity	NPC285931
0.8497	Intermediate Similarity	NPC290582
0.8497	Intermediate Similarity	NPC251735
0.8497	Intermediate Similarity	NPC182052
0.8497	Intermediate Similarity	NPC217748
0.8497	Intermediate Similarity	NPC229373
0.8497	Intermediate Similarity	NPC223690
0.8497	Intermediate Similarity	NPC104196
0.8497	Intermediate Similarity	NPC54654
0.8497	Intermediate Similarity	NPC290005
0.8497	Intermediate Similarity	NPC258657
0.8497	Intermediate Similarity	NPC239824
0.8497	Intermediate Similarity	NPC49075
0.8497	Intermediate Similarity	NPC181796
0.8497	Intermediate Similarity	NPC15414
0.8497	Intermediate Similarity	NPC90998
0.8497	Intermediate Similarity	NPC271013
0.8497	Intermediate Similarity	NPC311973
0.8462	Intermediate Similarity	NPC212237
0.8462	Intermediate Similarity	NPC116465
0.8454	Intermediate Similarity	NPC167116
0.8454	Intermediate Similarity	NPC274716
0.8454	Intermediate Similarity	NPC254441
0.8446	Intermediate Similarity	NPC286119
0.8434	Intermediate Similarity	NPC478091
0.8434	Intermediate Similarity	NPC473589
0.8434	Intermediate Similarity	NPC478092
0.8434	Intermediate Similarity	NPC30182
0.8384	Intermediate Similarity	NPC478093
0.8342	Intermediate Similarity	NPC256124
0.8325	Intermediate Similarity	NPC208890
0.8287	Intermediate Similarity	NPC315914
0.8283	Intermediate Similarity	NPC11296
0.8283	Intermediate Similarity	NPC48490
0.8283	Intermediate Similarity	NPC175890
0.8283	Intermediate Similarity	NPC274661
0.8283	Intermediate Similarity	NPC82457
0.8241	Intermediate Similarity	NPC60295
0.8241	Intermediate Similarity	NPC191132
0.82	Intermediate Similarity	NPC24260
0.815	Intermediate Similarity	NPC475597
0.815	Intermediate Similarity	NPC473716
0.8135	Intermediate Similarity	NPC276890
0.8135	Intermediate Similarity	NPC76682
0.8135	Intermediate Similarity	NPC115284
0.8135	Intermediate Similarity	NPC10908
0.8135	Intermediate Similarity	NPC317145
0.8135	Intermediate Similarity	NPC198498
0.8135	Intermediate Similarity	NPC227060
0.8135	Intermediate Similarity	NPC317439
0.8135	Intermediate Similarity	NPC63646
0.8103	Intermediate Similarity	NPC293093
0.8093	Intermediate Similarity	NPC12424
0.8093	Intermediate Similarity	NPC251580
0.8093	Intermediate Similarity	NPC129518
0.8093	Intermediate Similarity	NPC41376
0.8081	Intermediate Similarity	NPC302275
0.802	Intermediate Similarity	NPC32154
0.8019	Intermediate Similarity	NPC254581
0.8	Intermediate Similarity	NPC267414
0.8	Intermediate Similarity	NPC14507
0.8	Intermediate Similarity	NPC47077
0.799	Intermediate Similarity	NPC234318
0.799	Intermediate Similarity	NPC24228
0.798	Intermediate Similarity	NPC85381
0.797	Intermediate Similarity	NPC41122
0.797	Intermediate Similarity	NPC318805
0.7961	Intermediate Similarity	NPC469689
0.7961	Intermediate Similarity	NPC471031
0.7929	Intermediate Similarity	NPC243454
0.7929	Intermediate Similarity	NPC475479
0.7927	Intermediate Similarity	NPC240841
0.7927	Intermediate Similarity	NPC42549
0.7927	Intermediate Similarity	NPC317272
0.7927	Intermediate Similarity	NPC13916
0.7927	Intermediate Similarity	NPC268503
0.7927	Intermediate Similarity	NPC264850
0.7927	Intermediate Similarity	NPC256012
0.7927	Intermediate Similarity	NPC250846
0.7919	Intermediate Similarity	NPC222524
0.7919	Intermediate Similarity	NPC241704
0.7892	Intermediate Similarity	NPC316292
0.7892	Intermediate Similarity	NPC185031
0.7889	Intermediate Similarity	NPC239584
0.7885	Intermediate Similarity	NPC244191
0.7876	Intermediate Similarity	NPC24465
0.7864	Intermediate Similarity	NPC83019
0.785	Intermediate Similarity	NPC299990
0.785	Intermediate Similarity	NPC73492
0.7846	Intermediate Similarity	NPC204908
0.7846	Intermediate Similarity	NPC83198
0.7839	Intermediate Similarity	NPC99723
0.7837	Intermediate Similarity	NPC316164
0.7817	Intermediate Similarity	NPC190783
0.7817	Intermediate Similarity	NPC232386
0.7817	Intermediate Similarity	NPC152680
0.7816	Intermediate Similarity	NPC281629
0.7816	Intermediate Similarity	NPC204580
0.7789	Intermediate Similarity	NPC327005
0.7766	Intermediate Similarity	NPC239775
0.7766	Intermediate Similarity	NPC227683
0.7729	Intermediate Similarity	NPC279665
0.7723	Intermediate Similarity	NPC211215
0.772	Intermediate Similarity	NPC135006
0.7716	Intermediate Similarity	NPC168753
0.7716	Intermediate Similarity	NPC118274
0.7711	Intermediate Similarity	NPC257269
0.7711	Intermediate Similarity	NPC230276
0.77	Intermediate Similarity	NPC98583
0.7689	Intermediate Similarity	NPC314946
0.7685	Intermediate Similarity	NPC249996
0.7681	Intermediate Similarity	NPC477258
0.7677	Intermediate Similarity	NPC108434
0.7677	Intermediate Similarity	NPC475215
0.7664	Intermediate Similarity	NPC46990
0.7662	Intermediate Similarity	NPC40496
0.7662	Intermediate Similarity	NPC119068
0.7659	Intermediate Similarity	NPC82763
0.7659	Intermediate Similarity	NPC281581
0.7653	Intermediate Similarity	NPC314596
0.765	Intermediate Similarity	NPC100251
0.7647	Intermediate Similarity	NPC150977
0.7647	Intermediate Similarity	NPC162694
0.7647	Intermediate Similarity	NPC477259
0.7647	Intermediate Similarity	NPC169387
0.7635	Intermediate Similarity	NPC185275
0.7635	Intermediate Similarity	NPC324742
0.7633	Intermediate Similarity	NPC471563
0.7626	Intermediate Similarity	NPC43065
0.7624	Intermediate Similarity	NPC195538
0.7614	Intermediate Similarity	NPC205421
0.7614	Intermediate Similarity	NPC117188
0.7614	Intermediate Similarity	NPC145832
0.7614	Intermediate Similarity	NPC474931
0.7614	Intermediate Similarity	NPC81218
0.7614	Intermediate Similarity	NPC12053
0.7614	Intermediate Similarity	NPC306555
0.7614	Intermediate Similarity	NPC158376
0.761	Intermediate Similarity	NPC29531
0.7602	Intermediate Similarity	NPC44040
0.76	Intermediate Similarity	NPC180768
0.7598	Intermediate Similarity	NPC125352
0.7596	Intermediate Similarity	NPC264302
0.759	Intermediate Similarity	NPC80759
0.759	Intermediate Similarity	NPC79402
0.759	Intermediate Similarity	NPC60186
0.7586	Intermediate Similarity	NPC476202
0.7586	Intermediate Similarity	NPC265380
0.7583	Intermediate Similarity	NPC64576
0.7583	Intermediate Similarity	NPC254045
0.7583	Intermediate Similarity	NPC201055
0.7583	Intermediate Similarity	NPC151470
0.7576	Intermediate Similarity	NPC477840
0.7574	Intermediate Similarity	NPC474507
0.7565	Intermediate Similarity	NPC247639
0.7565	Intermediate Similarity	NPC25084
0.7562	Intermediate Similarity	NPC65333
0.7562	Intermediate Similarity	NPC4200
0.7561	Intermediate Similarity	NPC123259
0.7561	Intermediate Similarity	NPC129533
0.7559	Intermediate Similarity	NPC477666
0.755	Intermediate Similarity	NPC475212
0.7547	Intermediate Similarity	NPC202771
0.7547	Intermediate Similarity	NPC328700
0.7547	Intermediate Similarity	NPC2173
0.7547	Intermediate Similarity	NPC97086
0.7547	Intermediate Similarity	NPC119818
0.7547	Intermediate Similarity	NPC473660
0.7538	Intermediate Similarity	NPC230956
0.7538	Intermediate Similarity	NPC224851
0.7538	Intermediate Similarity	NPC272560
0.7538	Intermediate Similarity	NPC235143
0.7538	Intermediate Similarity	NPC119649
0.7538	Intermediate Similarity	NPC271388
0.7538	Intermediate Similarity	NPC205255
0.7537	Intermediate Similarity	NPC67629
0.7537	Intermediate Similarity	NPC79736
0.7537	Intermediate Similarity	NPC216307
0.7523	Intermediate Similarity	NPC80472
0.7523	Intermediate Similarity	NPC315253
0.7513	Intermediate Similarity	NPC13504
0.7513	Intermediate Similarity	NPC127674

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 NPC82056 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	227
0.1-0.2	708
0.2-0.3	1278
0.3-0.4	2137
0.4-0.5	2468
0.5-0.6	1598
0.6-0.7	594
0.7-0.8	136
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8497	Intermediate Similarity	NPD8054	Approved
0.8497	Intermediate Similarity	NPD8053	Approved
0.8317	Intermediate Similarity	NPD7501	Clinical (unspecified phase)
0.8209	Intermediate Similarity	NPD7667	Clinical (unspecified phase)
0.8187	Intermediate Similarity	NPD8156	Discontinued
0.8135	Intermediate Similarity	NPD8251	Approved
0.8135	Intermediate Similarity	NPD8099	Discontinued
0.8135	Intermediate Similarity	NPD8252	Approved
0.7972	Intermediate Similarity	NPD6997	Phase 2
0.7867	Intermediate Similarity	NPD7048	Phase 3
0.786	Intermediate Similarity	NPD7047	Phase 3
0.7844	Intermediate Similarity	NPD7907	Approved
0.7696	Intermediate Similarity	NPD6377	Clinical (unspecified phase)
0.7677	Intermediate Similarity	NPD7177	Discontinued
0.7662	Intermediate Similarity	NPD8453	Clinical (unspecified phase)
0.7583	Intermediate Similarity	NPD2494	Approved
0.7583	Intermediate Similarity	NPD3450	Approved
0.7583	Intermediate Similarity	NPD3452	Approved
0.7583	Intermediate Similarity	NPD2493	Approved
0.7547	Intermediate Similarity	NPD5006	Approved
0.7547	Intermediate Similarity	NPD5005	Approved
0.7512	Intermediate Similarity	NPD5676	Approved
0.7511	Intermediate Similarity	NPD4665	Approved
0.7511	Intermediate Similarity	NPD4111	Phase 1
0.7488	Intermediate Similarity	NPD7584	Approved
0.7477	Intermediate Similarity	NPD4583	Approved
0.7477	Intermediate Similarity	NPD4582	Approved
0.7476	Intermediate Similarity	NPD7291	Discontinued
0.7465	Intermediate Similarity	NPD3057	Approved
0.7465	Intermediate Similarity	NPD3448	Approved
0.7465	Intermediate Similarity	NPD2491	Approved
0.7458	Intermediate Similarity	NPD8153	Approved
0.7458	Intermediate Similarity	NPD8152	Approved
0.7455	Intermediate Similarity	NPD5619	Clinical (unspecified phase)
0.7454	Intermediate Similarity	NPD7701	Phase 2
0.743	Intermediate Similarity	NPD4004	Approved
0.743	Intermediate Similarity	NPD4002	Approved
0.7409	Intermediate Similarity	NPD1337	Clinical (unspecified phase)
0.7406	Intermediate Similarity	NPD8095	Phase 1
0.7404	Intermediate Similarity	NPD5525	Clinical (unspecified phase)
0.7404	Intermediate Similarity	NPD2490	Approved
0.7404	Intermediate Similarity	NPD3808	Clinical (unspecified phase)
0.7404	Intermediate Similarity	NPD2488	Approved
0.7393	Intermediate Similarity	NPD2975	Approved
0.7393	Intermediate Similarity	NPD2974	Approved
0.7393	Intermediate Similarity	NPD2973	Approved
0.7391	Intermediate Similarity	NPD7906	Approved
0.7383	Intermediate Similarity	NPD2972	Approved
0.7383	Intermediate Similarity	NPD3533	Approved
0.7373	Intermediate Similarity	NPD7585	Approved
0.7366	Intermediate Similarity	NPD8155	Clinical (unspecified phase)
0.7358	Intermediate Similarity	NPD4420	Approved
0.7358	Intermediate Similarity	NPD824	Approved
0.735	Intermediate Similarity	NPD5242	Approved
0.733	Intermediate Similarity	NPD6618	Phase 2
0.7327	Intermediate Similarity	NPD6973	Clinical (unspecified phase)
0.7327	Intermediate Similarity	NPD5940	Clinical (unspecified phase)
0.7327	Intermediate Similarity	NPD7583	Approved
0.7317	Intermediate Similarity	NPD4419	Clinical (unspecified phase)
0.7313	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7313	Intermediate Similarity	NPD6166	Phase 2
0.7313	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.731	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7304	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7291	Intermediate Similarity	NPD5313	Approved
0.7291	Intermediate Similarity	NPD5844	Phase 1
0.7291	Intermediate Similarity	NPD5312	Approved
0.729	Intermediate Similarity	NPD4580	Approved
0.7282	Intermediate Similarity	NPD3534	Clinical (unspecified phase)
0.7281	Intermediate Similarity	NPD8058	Clinical (unspecified phase)
0.7281	Intermediate Similarity	NPD8059	Phase 3
0.7273	Intermediate Similarity	NPD7782	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD8005	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD7783	Phase 2
0.726	Intermediate Similarity	NPD8151	Discontinued
0.726	Intermediate Similarity	NPD3863	Clinical (unspecified phase)
0.725	Intermediate Similarity	NPD6959	Discontinued
0.7243	Intermediate Similarity	NPD7810	Phase 3
0.7243	Intermediate Similarity	NPD7811	Phase 3
0.7233	Intermediate Similarity	NPD7549	Discontinued
0.722	Intermediate Similarity	NPD8149	Discontinued
0.7209	Intermediate Similarity	NPD4107	Approved
0.7208	Intermediate Similarity	NPD1465	Phase 2
0.7206	Intermediate Similarity	NPD6020	Phase 2
0.7198	Intermediate Similarity	NPD7942	Clinical (unspecified phase)
0.7194	Intermediate Similarity	NPD6386	Approved
0.7194	Intermediate Similarity	NPD6385	Approved
0.7189	Intermediate Similarity	NPD7064	Clinical (unspecified phase)
0.7178	Intermediate Similarity	NPD8051	Clinical (unspecified phase)
0.7174	Intermediate Similarity	NPD7654	Discontinued
0.717	Intermediate Similarity	NPD6181	Discontinued
0.7163	Intermediate Similarity	NPD6853	Approved
0.7163	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.7163	Intermediate Similarity	NPD6851	Approved
0.7163	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.715	Intermediate Similarity	NPD4584	Approved
0.715	Intermediate Similarity	NPD7132	Clinical (unspecified phase)
0.715	Intermediate Similarity	NPD5564	Approved
0.7143	Intermediate Similarity	NPD2898	Approved
0.7136	Intermediate Similarity	NPD6788	Approved
0.7129	Intermediate Similarity	NPD6232	Discontinued
0.7124	Intermediate Similarity	NPD6625	Approved
0.7124	Intermediate Similarity	NPD2899	Discontinued
0.7123	Intermediate Similarity	NPD7607	Clinical (unspecified phase)
0.7121	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7115	Intermediate Similarity	NPD2968	Approved
0.7115	Intermediate Similarity	NPD7311	Approved
0.7115	Intermediate Similarity	NPD7310	Approved
0.7115	Intermediate Similarity	NPD7313	Approved
0.7115	Intermediate Similarity	NPD2971	Approved
0.7115	Intermediate Similarity	NPD7312	Approved
0.711	Intermediate Similarity	NPD7497	Discontinued
0.7108	Intermediate Similarity	NPD7473	Discontinued
0.7097	Intermediate Similarity	NPD4482	Phase 3
0.7093	Intermediate Similarity	NPD7858	Clinical (unspecified phase)
0.7087	Intermediate Similarity	NPD7074	Phase 3
0.7087	Intermediate Similarity	NPD5441	Clinical (unspecified phase)
0.7085	Intermediate Similarity	NPD7827	Phase 1
0.7085	Intermediate Similarity	NPD5978	Approved
0.7085	Intermediate Similarity	NPD5977	Approved
0.7081	Intermediate Similarity	NPD7309	Approved
0.7078	Intermediate Similarity	NPD8319	Approved
0.7078	Intermediate Similarity	NPD8320	Phase 1
0.7078	Intermediate Similarity	NPD4040	Phase 1
0.7071	Intermediate Similarity	NPD1934	Approved
0.7062	Intermediate Similarity	NPD7693	Approved
0.7056	Intermediate Similarity	NPD4360	Phase 2
0.7056	Intermediate Similarity	NPD4363	Phase 3
0.7053	Intermediate Similarity	NPD6297	Approved
0.7051	Intermediate Similarity	NPD7922	Phase 1
0.7039	Intermediate Similarity	NPD7054	Approved
0.7035	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.7033	Intermediate Similarity	NPD4577	Approved
0.7033	Intermediate Similarity	NPD4578	Approved
0.7032	Intermediate Similarity	NPD7696	Phase 3
0.7032	Intermediate Similarity	NPD7698	Approved
0.7032	Intermediate Similarity	NPD7697	Approved
0.7028	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7024	Intermediate Similarity	NPD3446	Phase 1
0.702	Intermediate Similarity	NPD4772	Phase 2
0.702	Intermediate Similarity	NPD7109	Clinical (unspecified phase)
0.702	Intermediate Similarity	NPD4773	Phase 2
0.702	Intermediate Similarity	NPD7110	Phase 1
0.7015	Intermediate Similarity	NPD7833	Phase 2
0.7015	Intermediate Similarity	NPD7831	Phase 2
0.7015	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.7014	Intermediate Similarity	NPD4663	Approved
0.7005	Intermediate Similarity	NPD8285	Discontinued
0.7005	Intermediate Similarity	NPD7472	Approved
0.7	Intermediate Similarity	NPD7871	Phase 2
0.7	Intermediate Similarity	NPD7870	Phase 2
0.699	Remote Similarity	NPD3640	Phase 3
0.699	Remote Similarity	NPD3639	Approved
0.699	Remote Similarity	NPD3641	Approved
0.6986	Remote Similarity	NPD7190	Clinical (unspecified phase)
0.698	Remote Similarity	NPD8245	Clinical (unspecified phase)
0.6977	Remote Similarity	NPD4413	Clinical (unspecified phase)
0.6976	Remote Similarity	NPD7852	Clinical (unspecified phase)
0.6976	Remote Similarity	NPD2489	Approved
0.6976	Remote Similarity	NPD6894	Phase 1
0.6976	Remote Similarity	NPD27	Approved
0.6972	Remote Similarity	NPD6778	Approved
0.6972	Remote Similarity	NPD6777	Approved
0.6972	Remote Similarity	NPD6776	Approved
0.6972	Remote Similarity	NPD6780	Approved
0.6972	Remote Similarity	NPD6782	Approved
0.6972	Remote Similarity	NPD6781	Approved
0.6972	Remote Similarity	NPD6779	Approved
0.6964	Remote Similarity	NPD7801	Approved
0.6961	Remote Similarity	NPD6071	Discontinued
0.6961	Remote Similarity	NPD3051	Approved
0.6957	Remote Similarity	NPD3050	Clinical (unspecified phase)
0.6952	Remote Similarity	NPD6146	Clinical (unspecified phase)
0.695	Remote Similarity	NPD2801	Approved
0.695	Remote Similarity	NPD7819	Suspended
0.6946	Remote Similarity	NPD2904	Discontinued
0.6946	Remote Similarity	NPD5494	Approved
0.6944	Remote Similarity	NPD4361	Phase 2
0.6944	Remote Similarity	NPD4362	Clinical (unspecified phase)
0.6938	Remote Similarity	NPD7038	Approved
0.6938	Remote Similarity	NPD7039	Approved
0.6935	Remote Similarity	NPD7708	Approved
0.693	Remote Similarity	NPD4466	Phase 1
0.6927	Remote Similarity	NPD2969	Approved
0.6927	Remote Similarity	NPD2970	Approved
0.692	Remote Similarity	NPD7874	Approved
0.692	Remote Similarity	NPD7875	Clinical (unspecified phase)
0.6915	Remote Similarity	NPD5616	Clinical (unspecified phase)
0.6915	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6915	Remote Similarity	NPD5353	Approved
0.6909	Remote Similarity	NPD6823	Phase 2
0.6905	Remote Similarity	NPD7808	Phase 3
0.6904	Remote Similarity	NPD6662	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD6040	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD6608	Clinical (unspecified phase)
0.69	Remote Similarity	NPD7577	Discontinued
0.6898	Remote Similarity	NPD3473	Clinical (unspecified phase)
0.6892	Remote Similarity	NPD7803	Approved
0.6892	Remote Similarity	NPD8161	Suspended
0.689	Remote Similarity	NPD3823	Discontinued

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