NPASS Compound

Structure

NPC231371 OpenBabel07101719512D 23 26 0 0 1 0 0 0 0 0999 V2000 1.7321 -1.0000 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 3.4641 3.0000 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 2.5981 3.5000 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 0.8660 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4311 2.0243 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 1.7321 2.0000 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 0.0000 3.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3735 2.7930 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.0000 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 0.5000 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 0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7366 3.2272 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2395 3.2930 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 -0.0000 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 22 1 0 0 0 0 2 23 1 0 0 0 0 3 4 2 0 0 0 0 3 5 1 0 0 0 0 4 6 1 0 0 0 0 5 9 2 0 0 0 0 6 10 2 0 0 0 0 7 9 1 0 0 0 0 8 11 1 0 0 0 0 8 13 1 0 0 0 0 9 10 1 0 0 0 0 10 15 1 0 0 0 0 11 14 2 0 0 0 0 11 16 1 0 0 0 0 12 7 1 6 0 0 0 12 14 1 0 0 0 0 12 19 1 0 0 0 0 13 19 2 0 0 0 0 13 20 1 0 0 0 0 14 15 1 0 0 0 0 15 17 2 0 0 0 0 16 18 2 0 0 0 0 16 21 1 0 0 0 0 17 18 1 0 0 0 0 17 22 1 0 0 0 0 18 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	311.12
Volume:	313.361
LogP:	2.236
LogD:	2.02
LogS:	-2.82
# Rotatable Bonds:	2
TPSA:	67.79
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.893
Synthetic Accessibility Score:	3.228
Fsp3:	0.278
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-4.832
MDCK Permeability:	2.0062776457052678e-05
Pgp-inhibitor:	0.003
Pgp-substrate:	0.367
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.002

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.437
Plasma Protein Binding (PPB):	95.49713897705078%
Volume Distribution (VD):	0.663
Pgp-substrate:	4.35196590423584%

ADMET: Metabolism

CYP1A2-inhibitor:	0.265
CYP1A2-substrate:	0.802
CYP2C19-inhibitor:	0.29
CYP2C19-substrate:	0.805
CYP2C9-inhibitor:	0.557
CYP2C9-substrate:	0.882
CYP2D6-inhibitor:	0.15
CYP2D6-substrate:	0.256
CYP3A4-inhibitor:	0.56
CYP3A4-substrate:	0.833

ADMET: Excretion

Clearance (CL):	2.644
Half-life (T1/2):	0.581

ADMET: Toxicity

hERG Blockers:	0.042
Human Hepatotoxicity (H-HT):	0.706
Drug-inuced Liver Injury (DILI):	0.92
AMES Toxicity:	0.315
Rat Oral Acute Toxicity:	0.344
Maximum Recommended Daily Dose:	0.89
Skin Sensitization:	0.247
Carcinogencity:	0.095
Eye Corrosion:	0.003
Eye Irritation:	0.012
Respiratory Toxicity:	0.189

Download Data

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

Natural Product: NPC231371

Natural Product ID:	NPC231371
*Common Name:**	1,2-Dimethoxy-3-Hydroxy-5-Oxonoraporphine
IUPAC Name:	(6aR)-3-hydroxy-1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-5-one
Synonyms:
Standard InCHIKey:	YHTCCMRFBAMGJT-GFCCVEGCSA-N
Standard InCHI:	InChI=1S/C18H17NO4/c1-22-17-15-10-6-4-3-5-9(10)7-12-14(15)11(8-13(20)19-12)16(21)18(17)23-2/h3-6,12,21H,7-8H2,1-2H3,(H,19,20)/t12-/m1/s1
SMILES:	COc1c2-c3ccccc3C[C@@H]3c2c(CC(=N3)O)c(c1OC)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL491157
PubChem CID:	10662807
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0000381] Aporphines

*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
NPO32498	Mitrephora maingayi	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10479326]

☑ 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
ED50	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	ED50	>	30.0	mg/ml	PMID[495391]

☑ 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 NPC231371 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	344
0.1-0.2	1643
0.2-0.3	7648
0.3-0.4	10550
0.4-0.5	5165
0.5-0.6	9255
0.6-0.7	6516
0.7-0.8	1343
0.8-0.85	179
0.85-0.9	48
0.9-0.95	4
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9745	High Similarity	NPC68328
0.897	High Similarity	NPC168753
0.897	High Similarity	NPC118274
0.8944	High Similarity	NPC329837
0.8916	High Similarity	NPC239775
0.8765	High Similarity	NPC474507
0.8765	High Similarity	NPC206736
0.8765	High Similarity	NPC195766
0.8757	High Similarity	NPC476577
0.8757	High Similarity	NPC173416
0.8757	High Similarity	NPC148709
0.8735	High Similarity	NPC81218
0.8735	High Similarity	NPC205421
0.8735	High Similarity	NPC117188
0.8735	High Similarity	NPC145832
0.8735	High Similarity	NPC306555
0.8735	High Similarity	NPC12053
0.8735	High Similarity	NPC474931
0.8735	High Similarity	NPC158376
0.8639	High Similarity	NPC474051
0.8614	High Similarity	NPC136508
0.8614	High Similarity	NPC212794
0.8614	High Similarity	NPC253043
0.8614	High Similarity	NPC196447
0.8614	High Similarity	NPC13504
0.8614	High Similarity	NPC306843
0.8614	High Similarity	NPC96603
0.8614	High Similarity	NPC78222
0.8614	High Similarity	NPC477563
0.8554	High Similarity	NPC324144
0.8554	High Similarity	NPC1229
0.8529	High Similarity	NPC477020
0.8529	High Similarity	NPC192135
0.8529	High Similarity	NPC66341
0.8519	High Similarity	NPC275027
0.8514	High Similarity	NPC22928
0.8434	Intermediate Similarity	NPC166014
0.8434	Intermediate Similarity	NPC27410
0.8412	Intermediate Similarity	NPC477562
0.8412	Intermediate Similarity	NPC26240
0.8412	Intermediate Similarity	NPC69712
0.8395	Intermediate Similarity	NPC265473
0.8395	Intermediate Similarity	NPC276665
0.8382	Intermediate Similarity	NPC320223
0.8382	Intermediate Similarity	NPC114364
0.8371	Intermediate Similarity	NPC41122
0.8371	Intermediate Similarity	NPC318805
0.8362	Intermediate Similarity	NPC186546
0.8362	Intermediate Similarity	NPC476576
0.8352	Intermediate Similarity	NPC219170
0.8352	Intermediate Similarity	NPC180253
0.8343	Intermediate Similarity	NPC264850
0.8343	Intermediate Similarity	NPC276060
0.8343	Intermediate Similarity	NPC13916
0.8324	Intermediate Similarity	NPC478093
0.8315	Intermediate Similarity	NPC82763
0.8313	Intermediate Similarity	NPC476572
0.8305	Intermediate Similarity	NPC57036
0.8294	Intermediate Similarity	NPC204947
0.8287	Intermediate Similarity	NPC234318
0.8284	Intermediate Similarity	NPC24465
0.8278	Intermediate Similarity	NPC478091
0.8278	Intermediate Similarity	NPC85381
0.8278	Intermediate Similarity	NPC30182
0.8278	Intermediate Similarity	NPC478092
0.8278	Intermediate Similarity	NPC473589
0.8266	Intermediate Similarity	NPC199465
0.8266	Intermediate Similarity	NPC128560
0.8266	Intermediate Similarity	NPC229166
0.8235	Intermediate Similarity	NPC81247
0.8235	Intermediate Similarity	NPC476573
0.8235	Intermediate Similarity	NPC35627
0.8232	Intermediate Similarity	NPC52475
0.8232	Intermediate Similarity	NPC127402
0.8202	Intermediate Similarity	NPC214116
0.8193	Intermediate Similarity	NPC107602
0.8193	Intermediate Similarity	NPC99659
0.8193	Intermediate Similarity	NPC325871
0.8192	Intermediate Similarity	NPC135772
0.8182	Intermediate Similarity	NPC18614
0.8167	Intermediate Similarity	NPC294244
0.8166	Intermediate Similarity	NPC60186
0.8166	Intermediate Similarity	NPC79402
0.8166	Intermediate Similarity	NPC80759
0.8156	Intermediate Similarity	NPC22115
0.8156	Intermediate Similarity	NPC275680
0.815	Intermediate Similarity	NPC149090
0.815	Intermediate Similarity	NPC19520
0.814	Intermediate Similarity	NPC83198
0.814	Intermediate Similarity	NPC182257
0.814	Intermediate Similarity	NPC204908
0.8136	Intermediate Similarity	NPC28425
0.8107	Intermediate Similarity	NPC235143
0.8107	Intermediate Similarity	NPC119649
0.8107	Intermediate Similarity	NPC230956
0.8107	Intermediate Similarity	NPC205255
0.8107	Intermediate Similarity	NPC271388
0.8103	Intermediate Similarity	NPC190783
0.8103	Intermediate Similarity	NPC232386
0.8103	Intermediate Similarity	NPC152680
0.8101	Intermediate Similarity	NPC202846
0.8101	Intermediate Similarity	NPC143139
0.8079	Intermediate Similarity	NPC476574
0.8079	Intermediate Similarity	NPC32413
0.8079	Intermediate Similarity	NPC155442
0.8079	Intermediate Similarity	NPC119579
0.8079	Intermediate Similarity	NPC312918
0.8079	Intermediate Similarity	NPC477561
0.8079	Intermediate Similarity	NPC474506
0.8063	Intermediate Similarity	NPC308768
0.8063	Intermediate Similarity	NPC12668
0.805	Intermediate Similarity	NPC242715
0.805	Intermediate Similarity	NPC56329
0.805	Intermediate Similarity	NPC296898
0.8047	Intermediate Similarity	NPC221864
0.8045	Intermediate Similarity	NPC302245
0.8045	Intermediate Similarity	NPC95426
0.8045	Intermediate Similarity	NPC16357
0.8038	Intermediate Similarity	NPC241241
0.8038	Intermediate Similarity	NPC158142
0.8038	Intermediate Similarity	NPC294884
0.8038	Intermediate Similarity	NPC10314
0.8038	Intermediate Similarity	NPC200557
0.8038	Intermediate Similarity	NPC108198
0.8038	Intermediate Similarity	NPC69029
0.8034	Intermediate Similarity	NPC116284
0.8023	Intermediate Similarity	NPC470879
0.8023	Intermediate Similarity	NPC258695
0.8023	Intermediate Similarity	NPC192939
0.8023	Intermediate Similarity	NPC311936
0.8023	Intermediate Similarity	NPC215747
0.8022	Intermediate Similarity	NPC117717
0.8012	Intermediate Similarity	NPC326316
0.8012	Intermediate Similarity	NPC81733
0.8011	Intermediate Similarity	NPC112575
0.8	Intermediate Similarity	NPC289743
0.8	Intermediate Similarity	NPC275061
0.8	Intermediate Similarity	NPC218131
0.8	Intermediate Similarity	NPC243759
0.8	Intermediate Similarity	NPC212942
0.8	Intermediate Similarity	NPC139783
0.8	Intermediate Similarity	NPC220344
0.8	Intermediate Similarity	NPC132804
0.8	Intermediate Similarity	NPC29868
0.8	Intermediate Similarity	NPC105847
0.8	Intermediate Similarity	NPC110374
0.8	Intermediate Similarity	NPC79622
0.8	Intermediate Similarity	NPC65312
0.8	Intermediate Similarity	NPC243996
0.7987	Intermediate Similarity	NPC30632
0.7978	Intermediate Similarity	NPC286119
0.7978	Intermediate Similarity	NPC195538
0.7977	Intermediate Similarity	NPC298979
0.7977	Intermediate Similarity	NPC247389
0.7975	Intermediate Similarity	NPC160697
0.7975	Intermediate Similarity	NPC125649
0.7966	Intermediate Similarity	NPC260118
0.7966	Intermediate Similarity	NPC23219
0.7963	Intermediate Similarity	NPC175838
0.7963	Intermediate Similarity	NPC183709
0.7955	Intermediate Similarity	NPC329969
0.7937	Intermediate Similarity	NPC200935
0.7937	Intermediate Similarity	NPC266006
0.7937	Intermediate Similarity	NPC151656
0.7937	Intermediate Similarity	NPC230919
0.7937	Intermediate Similarity	NPC22902
0.7937	Intermediate Similarity	NPC266453
0.7933	Intermediate Similarity	NPC15414
0.7933	Intermediate Similarity	NPC239824
0.7933	Intermediate Similarity	NPC476202
0.7933	Intermediate Similarity	NPC182052
0.7933	Intermediate Similarity	NPC311973
0.7933	Intermediate Similarity	NPC258657
0.7933	Intermediate Similarity	NPC49075
0.7933	Intermediate Similarity	NPC30779
0.7933	Intermediate Similarity	NPC104196
0.7933	Intermediate Similarity	NPC223690
0.7933	Intermediate Similarity	NPC290005
0.7933	Intermediate Similarity	NPC90998
0.7933	Intermediate Similarity	NPC185639
0.7933	Intermediate Similarity	NPC285931
0.7933	Intermediate Similarity	NPC217748
0.7933	Intermediate Similarity	NPC328155
0.7933	Intermediate Similarity	NPC222661
0.7933	Intermediate Similarity	NPC251735
0.7933	Intermediate Similarity	NPC8836
0.7933	Intermediate Similarity	NPC54654
0.7933	Intermediate Similarity	NPC181796
0.7933	Intermediate Similarity	NPC229373
0.7933	Intermediate Similarity	NPC271013
0.7933	Intermediate Similarity	NPC290582
0.7933	Intermediate Similarity	NPC248642
0.7933	Intermediate Similarity	NPC42663
0.7933	Intermediate Similarity	NPC7715
0.7933	Intermediate Similarity	NPC279228
0.7925	Intermediate Similarity	NPC313081
0.7923	Intermediate Similarity	NPC476565
0.7919	Intermediate Similarity	NPC219341
0.7919	Intermediate Similarity	NPC476432
0.7919	Intermediate Similarity	NPC24264

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 NPC231371 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	210
0.1-0.2	780
0.2-0.3	1075
0.3-0.4	2333
0.4-0.5	2531
0.5-0.6	1561
0.6-0.7	556
0.7-0.8	101
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8323	Intermediate Similarity	NPD4055	Discovery
0.8232	Intermediate Similarity	NPD4005	Discontinued
0.7933	Intermediate Similarity	NPD8054	Approved
0.7933	Intermediate Similarity	NPD8053	Approved
0.7802	Intermediate Similarity	NPD7906	Approved
0.7791	Intermediate Similarity	NPD7975	Clinical (unspecified phase)
0.7785	Intermediate Similarity	NPD2674	Phase 3
0.7711	Intermediate Similarity	NPD2420	Approved
0.7711	Intermediate Similarity	NPD2421	Approved
0.768	Intermediate Similarity	NPD4578	Approved
0.768	Intermediate Similarity	NPD4577	Approved
0.765	Intermediate Similarity	NPD4663	Approved
0.7647	Intermediate Similarity	NPD4675	Approved
0.7647	Intermediate Similarity	NPD4678	Approved
0.7627	Intermediate Similarity	NPD2489	Approved
0.7627	Intermediate Similarity	NPD27	Approved
0.7614	Intermediate Similarity	NPD3051	Approved
0.761	Intermediate Similarity	NPD3144	Approved
0.761	Intermediate Similarity	NPD3145	Approved
0.7602	Intermediate Similarity	NPD5089	Approved
0.7602	Intermediate Similarity	NPD5090	Approved
0.76	Intermediate Similarity	NPD7201	Clinical (unspecified phase)
0.7582	Intermediate Similarity	NPD7313	Approved
0.7582	Intermediate Similarity	NPD7312	Approved
0.7582	Intermediate Similarity	NPD7311	Approved
0.7582	Intermediate Similarity	NPD7310	Approved
0.7571	Intermediate Similarity	NPD2970	Approved
0.7571	Intermediate Similarity	NPD2969	Approved
0.7542	Intermediate Similarity	NPD8099	Discontinued
0.7542	Intermediate Similarity	NPD8252	Approved
0.7542	Intermediate Similarity	NPD8251	Approved
0.7541	Intermediate Similarity	NPD7309	Approved
0.753	Intermediate Similarity	NPD6331	Phase 2
0.75	Intermediate Similarity	NPD8156	Discontinued
0.7456	Intermediate Similarity	NPD4584	Approved
0.7432	Intermediate Similarity	NPD8453	Clinical (unspecified phase)
0.7429	Intermediate Similarity	NPD6788	Approved
0.7425	Intermediate Similarity	NPD6658	Clinical (unspecified phase)
0.7424	Intermediate Similarity	NPD7827	Phase 1
0.7418	Intermediate Similarity	NPD6996	Clinical (unspecified phase)
0.7412	Intermediate Similarity	NPD5261	Clinical (unspecified phase)
0.741	Intermediate Similarity	NPD4664	Clinical (unspecified phase)
0.7381	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7381	Intermediate Similarity	NPD5241	Discontinued
0.7353	Intermediate Similarity	NPD4123	Phase 3
0.7348	Intermediate Similarity	NPD7493	Clinical (unspecified phase)
0.7329	Intermediate Similarity	NPD3027	Phase 3
0.7293	Intermediate Similarity	NPD5602	Clinical (unspecified phase)
0.7278	Intermediate Similarity	NPD1669	Approved
0.7268	Intermediate Similarity	NPD2494	Approved
0.7268	Intermediate Similarity	NPD3452	Approved
0.7268	Intermediate Similarity	NPD3450	Approved
0.7268	Intermediate Similarity	NPD2493	Approved
0.7238	Intermediate Similarity	NPD2898	Approved
0.7232	Intermediate Similarity	NPD4581	Clinical (unspecified phase)
0.7222	Intermediate Similarity	NPD4606	Clinical (unspecified phase)
0.7216	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.7207	Intermediate Similarity	NPD6746	Phase 2
0.72	Intermediate Similarity	NPD6072	Discontinued
0.7191	Intermediate Similarity	NPD7831	Phase 2
0.7191	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.7191	Intermediate Similarity	NPD7833	Phase 2
0.7184	Intermediate Similarity	NPD7261	Clinical (unspecified phase)
0.716	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7158	Intermediate Similarity	NPD2490	Approved
0.7158	Intermediate Similarity	NPD2488	Approved
0.7157	Intermediate Similarity	NPD4582	Approved
0.7157	Intermediate Similarity	NPD4583	Approved
0.7143	Intermediate Similarity	NPD2029	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD4481	Phase 3
0.7135	Intermediate Similarity	NPD3845	Phase 1
0.7135	Intermediate Similarity	NPD2422	Clinical (unspecified phase)
0.7134	Intermediate Similarity	NPD7477	Discontinued
0.7127	Intermediate Similarity	NPD4010	Discontinued
0.7112	Intermediate Similarity	NPD3534	Clinical (unspecified phase)
0.7107	Intermediate Similarity	NPD4002	Approved
0.7107	Intermediate Similarity	NPD4004	Approved
0.7099	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7093	Intermediate Similarity	NPD4357	Discontinued
0.7091	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7091	Intermediate Similarity	NPD1613	Approved
0.7079	Intermediate Similarity	NPD2563	Approved
0.7079	Intermediate Similarity	NPD2560	Approved
0.7077	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.7062	Intermediate Similarity	NPD2973	Approved
0.7062	Intermediate Similarity	NPD2974	Approved
0.7062	Intermediate Similarity	NPD2975	Approved
0.7053	Intermediate Similarity	NPD6843	Phase 3
0.7053	Intermediate Similarity	NPD6842	Approved
0.7053	Intermediate Similarity	NPD6841	Approved
0.7052	Intermediate Similarity	NPD4160	Clinical (unspecified phase)
0.7035	Intermediate Similarity	NPD7124	Phase 2
0.7024	Intermediate Similarity	NPD4108	Discontinued
0.7022	Intermediate Similarity	NPD5772	Approved
0.7022	Intermediate Similarity	NPD5773	Approved
0.7012	Intermediate Similarity	NPD1024	Discontinued
0.7012	Intermediate Similarity	NPD4625	Phase 3
0.7011	Intermediate Similarity	NPD7526	Approved
0.7011	Intermediate Similarity	NPD52	Approved
0.7011	Intermediate Similarity	NPD7527	Clinical (unspecified phase)
0.7006	Intermediate Similarity	NPD7438	Suspended
0.7	Intermediate Similarity	NPD7153	Discontinued
0.6984	Remote Similarity	NPD7090	Clinical (unspecified phase)
0.6982	Remote Similarity	NPD2161	Phase 2
0.6976	Remote Similarity	NPD7047	Phase 3
0.697	Remote Similarity	NPD4907	Clinical (unspecified phase)
0.6968	Remote Similarity	NPD7549	Discontinued
0.6959	Remote Similarity	NPD5177	Phase 3
0.6954	Remote Similarity	NPD7447	Phase 1
0.6954	Remote Similarity	NPD4580	Approved
0.6954	Remote Similarity	NPD1754	Clinical (unspecified phase)
0.694	Remote Similarity	NPD6232	Discontinued
0.694	Remote Similarity	NPD6071	Discontinued
0.6927	Remote Similarity	NPD2977	Approved
0.6927	Remote Similarity	NPD4585	Approved
0.6927	Remote Similarity	NPD2978	Approved
0.6915	Remote Similarity	NPD7263	Phase 2
0.691	Remote Similarity	NPD3778	Approved
0.6905	Remote Similarity	NPD1772	Clinical (unspecified phase)
0.6905	Remote Similarity	NPD4097	Suspended
0.6897	Remote Similarity	NPD7213	Phase 3
0.6897	Remote Similarity	NPD7212	Phase 2
0.6893	Remote Similarity	NPD4017	Approved
0.6886	Remote Similarity	NPD3109	Approved
0.6886	Remote Similarity	NPD3110	Approved
0.6879	Remote Similarity	NPD302	Approved
0.6879	Remote Similarity	NPD2219	Phase 1
0.6875	Remote Similarity	NPD7243	Clinical (unspecified phase)
0.6872	Remote Similarity	NPD7298	Approved
0.6868	Remote Similarity	NPD6234	Discontinued
0.686	Remote Similarity	NPD3060	Approved
0.6857	Remote Similarity	NPD1424	Approved
0.6857	Remote Similarity	NPD6997	Phase 2
0.6854	Remote Similarity	NPD5617	Suspended
0.6854	Remote Similarity	NPD6502	Phase 2
0.6848	Remote Similarity	NPD4908	Phase 1
0.6845	Remote Similarity	NPD6042	Phase 2
0.6845	Remote Similarity	NPD42	Phase 2
0.6842	Remote Similarity	NPD5917	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD2971	Approved
0.6842	Remote Similarity	NPD1375	Discontinued
0.6842	Remote Similarity	NPD2968	Approved
0.6831	Remote Similarity	NPD4666	Phase 3
0.6828	Remote Similarity	NPD7473	Discontinued
0.6818	Remote Similarity	NPD6090	Discontinued
0.6818	Remote Similarity	NPD8095	Phase 1
0.6816	Remote Similarity	NPD4773	Phase 2
0.6816	Remote Similarity	NPD4772	Phase 2
0.6811	Remote Similarity	NPD4083	Discontinued
0.6805	Remote Similarity	NPD2157	Approved
0.6786	Remote Similarity	NPD2238	Phase 2
0.6782	Remote Similarity	NPD5084	Clinical (unspecified phase)
0.6782	Remote Similarity	NPD3692	Discontinued
0.678	Remote Similarity	NPD6030	Approved
0.678	Remote Similarity	NPD2122	Discontinued
0.678	Remote Similarity	NPD6031	Approved
0.6778	Remote Similarity	NPD37	Approved
0.6776	Remote Similarity	NPD5709	Phase 3
0.6772	Remote Similarity	NPD7007	Discovery
0.6766	Remote Similarity	NPD5110	Phase 2
0.6766	Remote Similarity	NPD5111	Phase 2
0.6766	Remote Similarity	NPD5109	Approved
0.6763	Remote Similarity	NPD6674	Discontinued
0.6755	Remote Similarity	NPD5844	Phase 1
0.6751	Remote Similarity	NPD7667	Clinical (unspecified phase)
0.6748	Remote Similarity	NPD3676	Clinical (unspecified phase)
0.674	Remote Similarity	NPD5929	Approved
0.6738	Remote Similarity	NPD3489	Phase 3
0.6726	Remote Similarity	NPD839	Approved
0.6726	Remote Similarity	NPD840	Approved
0.6726	Remote Similarity	NPD4474	Approved
0.6726	Remote Similarity	NPD4475	Approved
0.6725	Remote Similarity	NPD6029	Clinical (unspecified phase)
0.6725	Remote Similarity	NPD6028	Clinical (unspecified phase)
0.6723	Remote Similarity	NPD3647	Clinical (unspecified phase)
0.6722	Remote Similarity	NPD3796	Clinical (unspecified phase)
0.6721	Remote Similarity	NPD5604	Discontinued
0.6721	Remote Similarity	NPD8070	Approved
0.6717	Remote Similarity	NPD4605	Approved
0.6717	Remote Similarity	NPD4604	Approved
0.6716	Remote Similarity	NPD7590	Clinical (unspecified phase)
0.6707	Remote Similarity	NPD5155	Approved
0.6707	Remote Similarity	NPD2669	Clinical (unspecified phase)
0.6707	Remote Similarity	NPD5156	Approved
0.6707	Remote Similarity	NPD2922	Phase 1
0.6704	Remote Similarity	NPD6523	Clinical (unspecified phase)
0.6702	Remote Similarity	NPD7228	Approved
0.6687	Remote Similarity	NPD3018	Phase 2
0.6686	Remote Similarity	NPD3619	Clinical (unspecified phase)
0.6686	Remote Similarity	NPD1558	Phase 1
0.6686	Remote Similarity	NPD3620	Phase 2
0.6686	Remote Similarity	NPD1632	Clinical (unspecified phase)
0.6685	Remote Similarity	NPD3640	Phase 3
0.6685	Remote Similarity	NPD3639	Approved
0.6685	Remote Similarity	NPD3641	Approved
0.6684	Remote Similarity	NPD5822	Clinical (unspecified phase)
0.6684	Remote Similarity	NPD6184	Discontinued
0.6683	Remote Similarity	NPD8151	Discontinued
0.6667	Remote Similarity	NPD3296	Phase 1
0.6667	Remote Similarity	NPD4237	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