NPASS Compound

Structure

NPC269270 OpenBabel07101719242D 27 30 0 0 0 0 0 0 0 0999 V2000 1.1845 5.6703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9487 2.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8147 1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8147 3.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6808 1.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2113 4.5477 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2168 4.6522 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5962 3.4263 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9781 0.2079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3978 6.3748 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9487 1.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6180 3.6342 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6808 2.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0827 1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1180 2.7681 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1691 1.6092 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7872 2.0250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1399 2.5602 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4781 1.0739 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7007 2.4317 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 0.1900 5.5658 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0089 7.2883 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5468 3.2024 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5292 3.3034 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1473 0.3308 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 23 1 0 0 0 0 2 4 1 0 0 0 0 2 11 2 0 0 0 0 3 5 2 0 0 0 0 3 11 1 0 0 0 0 4 13 2 0 0 0 0 5 13 1 0 0 0 0 6 7 1 0 0 0 0 6 12 1 0 0 0 0 7 23 1 0 0 0 0 8 12 2 0 0 0 0 8 21 1 0 0 0 0 9 14 2 0 0 0 0 9 22 1 0 0 0 0 10 23 1 0 0 0 0 10 24 2 0 0 0 0 11 14 1 0 0 0 0 12 15 1 0 0 0 0 13 25 1 0 0 0 0 14 16 1 0 0 0 0 15 17 2 0 0 0 0 15 19 1 0 0 0 0 16 18 2 0 0 0 0 16 19 1 0 0 0 0 17 20 1 0 0 0 0 17 21 1 0 0 0 0 18 20 1 0 0 0 0 18 22 1 0 0 0 0 19 26 2 0 0 0 0 20 27 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	363.12
Volume:	362.037
LogP:	3.959
LogD:	2.488
LogS:	-4.858
# Rotatable Bonds:	4
TPSA:	112.58
# H-Bond Aceptor:	7
# H-Bond Donor:	5
# Rings:	4
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.282
Synthetic Accessibility Score:	3.38
Fsp3:	0.05
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.232
MDCK Permeability:	3.36226048602839e-06
Pgp-inhibitor:	0.0
Pgp-substrate:	0.153
Human Intestinal Absorption (HIA):	0.031
20% Bioavailability (F20%):	0.905
30% Bioavailability (F30%):	0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.014
Plasma Protein Binding (PPB):	95.55008697509766%
Volume Distribution (VD):	0.975
Pgp-substrate:	4.41530704498291%

ADMET: Metabolism

CYP1A2-inhibitor:	0.958
CYP1A2-substrate:	0.644
CYP2C19-inhibitor:	0.691
CYP2C19-substrate:	0.048
CYP2C9-inhibitor:	0.848
CYP2C9-substrate:	0.976
CYP2D6-inhibitor:	0.834
CYP2D6-substrate:	0.887
CYP3A4-inhibitor:	0.261
CYP3A4-substrate:	0.108

ADMET: Excretion

Clearance (CL):	6.049
Half-life (T1/2):	0.84

ADMET: Toxicity

hERG Blockers:	0.048
Human Hepatotoxicity (H-HT):	0.325
Drug-inuced Liver Injury (DILI):	0.97
AMES Toxicity:	0.261
Rat Oral Acute Toxicity:	0.942
Maximum Recommended Daily Dose:	0.608
Skin Sensitization:	0.683
Carcinogencity:	0.195
Eye Corrosion:	0.003
Eye Irritation:	0.03
Respiratory Toxicity:	0.179

Download Data

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

Natural Product: NPC269270

Natural Product ID:	NPC269270
*Common Name:**	Zyzzyanone D
IUPAC Name:	N-[2-[3-(4-hydroxyphenyl)-4,8-dioxo-1,7-dihydropyrrolo[3,2-f]indol-5-yl]ethyl]-N-methylformamide
Synonyms:	Zyzzyanone D
Standard InCHIKey:	OBNMCBPRQYXKOU-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C20H17N3O4/c1-23(10-24)7-6-12-8-21-17-15(12)19(26)16-14(9-22-18(16)20(17)27)11-2-4-13(25)5-3-11/h2-5,8-10,21-22,25H,6-7H2,1H3
SMILES:	O=CN(CCc1c[nH]c2c1c(=O)c1c(c[nH]c1c2=O)c1ccc(cc1)O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL463287
PubChem CID:	11717517
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0001733] Pyrroloindoles

*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
NPO32549	zyzzya fuliginosa	Species	n.a.	Eukaryota	n.a.	indopacific	n.a.	PMID[12027767]
NPO32549	zyzzya fuliginosa	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	PMID[16180829]
NPO32549	zyzzya fuliginosa	Species	n.a.	Eukaryota	n.a.	pohnpeian	n.a.	PMID[8691207]
NPO32549	zyzzya fuliginosa	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	PMID[9134749]

☑ 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

Activity Type	# Activity
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	25.0	ug.mL-1	PMID[488940]

☑ 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 NPC269270 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	384
0.1-0.2	2847
0.2-0.3	13446
0.3-0.4	6846
0.4-0.5	14087
0.5-0.6	2987
0.6-0.7	1885
0.7-0.8	202
0.8-0.85	7
0.85-0.9	1
0.9-0.95	2
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9949	High Similarity	NPC14686
0.959	High Similarity	NPC110182
0.9141	High Similarity	NPC61038
0.9086	High Similarity	NPC175602
0.896	High Similarity	NPC207866
0.8263	Intermediate Similarity	NPC276657
0.8218	Intermediate Similarity	NPC74153
0.8159	Intermediate Similarity	NPC473821
0.8128	Intermediate Similarity	NPC473814
0.8128	Intermediate Similarity	NPC78767
0.8119	Intermediate Similarity	NPC93390
0.8075	Intermediate Similarity	NPC322064
0.8037	Intermediate Similarity	NPC27041
0.8	Intermediate Similarity	NPC264285
0.7892	Intermediate Similarity	NPC207686
0.7854	Intermediate Similarity	NPC16352
0.7832	Intermediate Similarity	NPC15801
0.7789	Intermediate Similarity	NPC271792
0.7783	Intermediate Similarity	NPC183777
0.7749	Intermediate Similarity	NPC178858
0.7719	Intermediate Similarity	NPC101350
0.7707	Intermediate Similarity	NPC476460
0.7682	Intermediate Similarity	NPC63971
0.7682	Intermediate Similarity	NPC91868
0.7675	Intermediate Similarity	NPC235685
0.7668	Intermediate Similarity	NPC24370
0.7668	Intermediate Similarity	NPC319232
0.7664	Intermediate Similarity	NPC171787
0.7658	Intermediate Similarity	NPC229893
0.7644	Intermediate Similarity	NPC326363
0.7639	Intermediate Similarity	NPC82370
0.7632	Intermediate Similarity	NPC477549
0.7626	Intermediate Similarity	NPC472285
0.7623	Intermediate Similarity	NPC476818
0.7608	Intermediate Similarity	NPC227582
0.7604	Intermediate Similarity	NPC219087
0.7602	Intermediate Similarity	NPC323969
0.76	Intermediate Similarity	NPC194740
0.7588	Intermediate Similarity	NPC325976
0.7577	Intermediate Similarity	NPC279189
0.7577	Intermediate Similarity	NPC200553
0.7577	Intermediate Similarity	NPC196718
0.7535	Intermediate Similarity	NPC270918
0.75	Intermediate Similarity	NPC252338
0.75	Intermediate Similarity	NPC471448
0.75	Intermediate Similarity	NPC122436
0.75	Intermediate Similarity	NPC102593
0.75	Intermediate Similarity	NPC56170
0.7488	Intermediate Similarity	NPC131887
0.7478	Intermediate Similarity	NPC162002
0.7467	Intermediate Similarity	NPC323752
0.7465	Intermediate Similarity	NPC471944
0.7463	Intermediate Similarity	NPC295158
0.7458	Intermediate Similarity	NPC63109
0.7455	Intermediate Similarity	NPC237740
0.7453	Intermediate Similarity	NPC74413
0.7435	Intermediate Similarity	NPC174489
0.7421	Intermediate Similarity	NPC36405
0.7418	Intermediate Similarity	NPC213308
0.7416	Intermediate Similarity	NPC99666
0.7415	Intermediate Similarity	NPC477003
0.7399	Intermediate Similarity	NPC74360
0.7397	Intermediate Similarity	NPC23294
0.7395	Intermediate Similarity	NPC134848
0.7395	Intermediate Similarity	NPC317701
0.7389	Intermediate Similarity	NPC67659
0.7381	Intermediate Similarity	NPC304203
0.7379	Intermediate Similarity	NPC311282
0.7371	Intermediate Similarity	NPC184225
0.7371	Intermediate Similarity	NPC26641
0.7359	Intermediate Similarity	NPC182222
0.7355	Intermediate Similarity	NPC74619
0.7352	Intermediate Similarity	NPC303951
0.7349	Intermediate Similarity	NPC260900
0.734	Intermediate Similarity	NPC284775
0.7336	Intermediate Similarity	NPC45459
0.7336	Intermediate Similarity	NPC315491
0.7333	Intermediate Similarity	NPC473317
0.7331	Intermediate Similarity	NPC78609
0.7308	Intermediate Similarity	NPC278434
0.7308	Intermediate Similarity	NPC37152
0.7304	Intermediate Similarity	NPC477112
0.7284	Intermediate Similarity	NPC97902
0.7265	Intermediate Similarity	NPC330009
0.726	Intermediate Similarity	NPC86834
0.726	Intermediate Similarity	NPC210828
0.726	Intermediate Similarity	NPC39679
0.7253	Intermediate Similarity	NPC473187
0.7251	Intermediate Similarity	NPC324149
0.7241	Intermediate Similarity	NPC70155
0.724	Intermediate Similarity	NPC9894
0.7237	Intermediate Similarity	NPC125597
0.7232	Intermediate Similarity	NPC293151
0.7229	Intermediate Similarity	NPC260434
0.7225	Intermediate Similarity	NPC220851
0.7225	Intermediate Similarity	NPC206186
0.7222	Intermediate Similarity	NPC100104
0.7222	Intermediate Similarity	NPC300183
0.7222	Intermediate Similarity	NPC470680
0.7202	Intermediate Similarity	NPC472259
0.7202	Intermediate Similarity	NPC53534
0.72	Intermediate Similarity	NPC303658
0.7196	Intermediate Similarity	NPC77555
0.7196	Intermediate Similarity	NPC156704
0.7195	Intermediate Similarity	NPC309845
0.719	Intermediate Similarity	NPC244543
0.719	Intermediate Similarity	NPC314882
0.7185	Intermediate Similarity	NPC208522
0.7177	Intermediate Similarity	NPC171171
0.7174	Intermediate Similarity	NPC478078
0.7168	Intermediate Similarity	NPC48317
0.7167	Intermediate Similarity	NPC220852
0.7163	Intermediate Similarity	NPC472284
0.7156	Intermediate Similarity	NPC83111
0.7156	Intermediate Similarity	NPC154339
0.7149	Intermediate Similarity	NPC28945
0.7149	Intermediate Similarity	NPC240384
0.7149	Intermediate Similarity	NPC153400
0.7143	Intermediate Similarity	NPC46580
0.7137	Intermediate Similarity	NPC150239
0.7136	Intermediate Similarity	NPC326422
0.7136	Intermediate Similarity	NPC267343
0.7136	Intermediate Similarity	NPC283117
0.7136	Intermediate Similarity	NPC88008
0.7131	Intermediate Similarity	NPC148889
0.7129	Intermediate Similarity	NPC314002
0.7129	Intermediate Similarity	NPC241025
0.7124	Intermediate Similarity	NPC132329
0.7123	Intermediate Similarity	NPC138370
0.7119	Intermediate Similarity	NPC41679
0.7117	Intermediate Similarity	NPC11464
0.7111	Intermediate Similarity	NPC469928
0.711	Intermediate Similarity	NPC328596
0.711	Intermediate Similarity	NPC328318
0.7109	Intermediate Similarity	NPC209917
0.7109	Intermediate Similarity	NPC196449
0.7109	Intermediate Similarity	NPC321708
0.7109	Intermediate Similarity	NPC314222
0.7105	Intermediate Similarity	NPC60621
0.7104	Intermediate Similarity	NPC266249
0.7102	Intermediate Similarity	NPC475746
0.7102	Intermediate Similarity	NPC258048
0.7093	Intermediate Similarity	NPC168209
0.7093	Intermediate Similarity	NPC288987
0.7085	Intermediate Similarity	NPC474492
0.7085	Intermediate Similarity	NPC87413
0.7083	Intermediate Similarity	NPC306376
0.7083	Intermediate Similarity	NPC477041
0.7083	Intermediate Similarity	NPC67288
0.7083	Intermediate Similarity	NPC477044
0.7081	Intermediate Similarity	NPC204717
0.708	Intermediate Similarity	NPC469727
0.708	Intermediate Similarity	NPC305984
0.7076	Intermediate Similarity	NPC285343
0.7075	Intermediate Similarity	NPC77101
0.7072	Intermediate Similarity	NPC478158
0.7067	Intermediate Similarity	NPC478157
0.7067	Intermediate Similarity	NPC474412
0.7064	Intermediate Similarity	NPC475635
0.7056	Intermediate Similarity	NPC214142
0.7054	Intermediate Similarity	NPC471193
0.7054	Intermediate Similarity	NPC153980
0.7054	Intermediate Similarity	NPC471194
0.7054	Intermediate Similarity	NPC6865
0.7054	Intermediate Similarity	NPC12344
0.7051	Intermediate Similarity	NPC49547
0.7051	Intermediate Similarity	NPC477045
0.7051	Intermediate Similarity	NPC473186
0.7048	Intermediate Similarity	NPC133003
0.7048	Intermediate Similarity	NPC247803
0.7045	Intermediate Similarity	NPC475070
0.7045	Intermediate Similarity	NPC470500
0.7045	Intermediate Similarity	NPC477043
0.704	Intermediate Similarity	NPC123839
0.704	Intermediate Similarity	NPC124086
0.7037	Intermediate Similarity	NPC90229
0.7035	Intermediate Similarity	NPC3207
0.7033	Intermediate Similarity	NPC220765
0.7032	Intermediate Similarity	NPC476073
0.7032	Intermediate Similarity	NPC57398
0.7029	Intermediate Similarity	NPC171393
0.7029	Intermediate Similarity	NPC295452
0.7029	Intermediate Similarity	NPC473312
0.7028	Intermediate Similarity	NPC152620
0.7028	Intermediate Similarity	NPC221873
0.7027	Intermediate Similarity	NPC127677
0.7027	Intermediate Similarity	NPC258062
0.7026	Intermediate Similarity	NPC261251
0.7026	Intermediate Similarity	NPC304307
0.7026	Intermediate Similarity	NPC118559
0.7026	Intermediate Similarity	NPC124920
0.7026	Intermediate Similarity	NPC34580
0.7023	Intermediate Similarity	NPC202812
0.7022	Intermediate Similarity	NPC266931
0.7021	Intermediate Similarity	NPC284888
0.7014	Intermediate Similarity	NPC472287
0.7014	Intermediate Similarity	NPC94752
0.7014	Intermediate Similarity	NPC317373
0.7014	Intermediate Similarity	NPC472286
0.7009	Intermediate Similarity	NPC119006

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 NPC269270 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	214
0.1-0.2	651
0.2-0.3	859
0.3-0.4	1290
0.4-0.5	3046
0.5-0.6	2319
0.6-0.7	746
0.7-0.8	25
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7915	Intermediate Similarity	NPD6376	Discontinued
0.7752	Intermediate Similarity	NPD8405	Clinical (unspecified phase)
0.7634	Intermediate Similarity	NPD4845	Discontinued
0.7621	Intermediate Similarity	NPD5040	Clinical (unspecified phase)
0.7523	Intermediate Similarity	NPD5901	Discontinued
0.7511	Intermediate Similarity	NPD7603	Discontinued
0.7425	Intermediate Similarity	NPD6790	Phase 1
0.7397	Intermediate Similarity	NPD7470	Discontinued
0.7371	Intermediate Similarity	NPD4958	Clinical (unspecified phase)
0.7366	Intermediate Similarity	NPD6242	Discontinued
0.7361	Intermediate Similarity	NPD3947	Discontinued
0.7358	Intermediate Similarity	NPD7948	Phase 1
0.7339	Intermediate Similarity	NPD2510	Approved
0.7339	Intermediate Similarity	NPD2509	Approved
0.7336	Intermediate Similarity	NPD484	Approved
0.7336	Intermediate Similarity	NPD5801	Clinical (unspecified phase)
0.7217	Intermediate Similarity	NPD5575	Clinical (unspecified phase)
0.7215	Intermediate Similarity	NPD6838	Clinical (unspecified phase)
0.7202	Intermediate Similarity	NPD5426	Phase 3
0.7179	Intermediate Similarity	NPD3006	Discontinued
0.7168	Intermediate Similarity	NPD7203	Clinical (unspecified phase)
0.715	Intermediate Similarity	NPD3178	Discontinued
0.7143	Intermediate Similarity	NPD4948	Discontinued
0.713	Intermediate Similarity	NPD6999	Discontinued
0.713	Intermediate Similarity	NPD7000	Clinical (unspecified phase)
0.7124	Intermediate Similarity	NPD4429	Discontinued
0.7123	Intermediate Similarity	NPD5592	Clinical (unspecified phase)
0.7117	Intermediate Similarity	NPD7998	Clinical (unspecified phase)
0.7111	Intermediate Similarity	NPD3393	Approved
0.7111	Intermediate Similarity	NPD3394	Approved
0.7111	Intermediate Similarity	NPD3389	Approved
0.7091	Intermediate Similarity	NPD6732	Clinical (unspecified phase)
0.7091	Intermediate Similarity	NPD7001	Phase 3
0.7085	Intermediate Similarity	NPD8013	Clinical (unspecified phase)
0.7078	Intermediate Similarity	NPD2121	Clinical (unspecified phase)
0.7054	Intermediate Similarity	NPD4852	Phase 2
0.7042	Intermediate Similarity	NPD6180	Clinical (unspecified phase)
0.7029	Intermediate Similarity	NPD3914	Clinical (unspecified phase)
0.7012	Intermediate Similarity	NPD7393	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD8356	Approved
0.7	Intermediate Similarity	NPD6995	Phase 1
0.7	Intermediate Similarity	NPD3607	Clinical (unspecified phase)
0.699	Remote Similarity	NPD5065	Approved
0.6987	Remote Similarity	NPD1996	Discontinued
0.6986	Remote Similarity	NPD4511	Phase 1
0.6979	Remote Similarity	NPD3746	Discontinued
0.6978	Remote Similarity	NPD8093	Discontinued
0.6976	Remote Similarity	NPD6531	Approved
0.6976	Remote Similarity	NPD6530	Approved
0.6971	Remote Similarity	NPD5483	Clinical (unspecified phase)
0.697	Remote Similarity	NPD7547	Clinical (unspecified phase)
0.6968	Remote Similarity	NPD6987	Phase 1
0.6967	Remote Similarity	NPD6344	Clinical (unspecified phase)
0.6966	Remote Similarity	NPD5022	Discontinued
0.6962	Remote Similarity	NPD7853	Phase 2
0.6955	Remote Similarity	NPD4558	Phase 2
0.6953	Remote Similarity	NPD8430	Approved
0.6951	Remote Similarity	NPD7666	Phase 3
0.6951	Remote Similarity	NPD7665	Phase 2
0.6947	Remote Similarity	NPD8094	Discontinued
0.6946	Remote Similarity	NPD2921	Clinical (unspecified phase)
0.6937	Remote Similarity	NPD3507	Phase 2
0.6937	Remote Similarity	NPD4862	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD6567	Clinical (unspecified phase)
0.693	Remote Similarity	NPD3326	Clinical (unspecified phase)
0.693	Remote Similarity	NPD4922	Phase 2
0.693	Remote Similarity	NPD7823	Clinical (unspecified phase)
0.692	Remote Similarity	NPD8349	Phase 1
0.6903	Remote Similarity	NPD5866	Approved
0.6903	Remote Similarity	NPD8096	Phase 3
0.6903	Remote Similarity	NPD8097	Phase 3
0.6895	Remote Similarity	NPD6137	Clinical (unspecified phase)
0.6895	Remote Similarity	NPD7621	Clinical (unspecified phase)
0.6886	Remote Similarity	NPD5612	Discontinued
0.688	Remote Similarity	NPD3259	Approved
0.688	Remote Similarity	NPD7994	Phase 2
0.6878	Remote Similarity	NPD4373	Phase 2
0.6857	Remote Similarity	NPD5482	Discontinued
0.6857	Remote Similarity	NPD3809	Discontinued
0.6856	Remote Similarity	NPD2813	Phase 3
0.6856	Remote Similarity	NPD8000	Clinical (unspecified phase)
0.6856	Remote Similarity	NPD2812	Clinical (unspecified phase)
0.6853	Remote Similarity	NPD6824	Clinical (unspecified phase)
0.6845	Remote Similarity	NPD1573	Approved
0.6845	Remote Similarity	NPD1575	Approved
0.6842	Remote Similarity	NPD5293	Phase 2
0.684	Remote Similarity	NPD2091	Phase 2
0.684	Remote Similarity	NPD2096	Phase 2
0.6838	Remote Similarity	NPD3263	Phase 3
0.6835	Remote Similarity	NPD3960	Clinical (unspecified phase)
0.6835	Remote Similarity	NPD4885	Approved
0.6835	Remote Similarity	NPD4848	Phase 1
0.6831	Remote Similarity	NPD3962	Phase 2
0.6831	Remote Similarity	NPD3959	Phase 2
0.683	Remote Similarity	NPD8493	Clinical (unspecified phase)
0.6828	Remote Similarity	NPD3916	Clinical (unspecified phase)
0.6828	Remote Similarity	NPD3918	Approved
0.6828	Remote Similarity	NPD3917	Approved
0.6828	Remote Similarity	NPD2411	Approved
0.6827	Remote Similarity	NPD8091	Phase 3
0.6826	Remote Similarity	NPD7878	Phase 2
0.6822	Remote Similarity	NPD4952	Phase 3
0.682	Remote Similarity	NPD1038	Approved
0.681	Remote Similarity	NPD4923	Phase 1
0.6809	Remote Similarity	NPD6164	Phase 2
0.6809	Remote Similarity	NPD6165	Phase 2
0.6808	Remote Similarity	NPD6610	Clinical (unspecified phase)
0.68	Remote Similarity	NPD3801	Clinical (unspecified phase)
0.68	Remote Similarity	NPD2916	Discontinued
0.6798	Remote Similarity	NPD3243	Approved
0.6794	Remote Similarity	NPD749	Clinical (unspecified phase)
0.6793	Remote Similarity	NPD7688	Phase 1
0.6792	Remote Similarity	NPD5728	Clinical (unspecified phase)
0.6792	Remote Similarity	NPD2092	Phase 2
0.6792	Remote Similarity	NPD2094	Phase 2
0.6792	Remote Similarity	NPD2095	Phase 2
0.6789	Remote Similarity	NPD7619	Phase 3
0.6789	Remote Similarity	NPD7618	Phase 3
0.6789	Remote Similarity	NPD5975	Clinical (unspecified phase)
0.6787	Remote Similarity	NPD8248	Clinical (unspecified phase)
0.6786	Remote Similarity	NPD2008	Discontinued
0.6784	Remote Similarity	NPD3915	Approved
0.6777	Remote Similarity	NPD6595	Phase 3
0.6777	Remote Similarity	NPD1643	Phase 3
0.6774	Remote Similarity	NPD6665	Discontinued
0.6771	Remote Similarity	NPD6176	Phase 1
0.6769	Remote Similarity	NPD7181	Phase 3
0.6769	Remote Similarity	NPD3757	Clinical (unspecified phase)
0.6766	Remote Similarity	NPD8289	Discontinued
0.6759	Remote Similarity	NPD6456	Discontinued
0.6757	Remote Similarity	NPD5017	Discontinued
0.6754	Remote Similarity	NPD3330	Phase 1
0.6754	Remote Similarity	NPD7594	Clinical (unspecified phase)
0.6746	Remote Similarity	NPD482	Approved
0.6745	Remote Similarity	NPD1783	Clinical (unspecified phase)
0.6743	Remote Similarity	NPD802	Phase 2
0.6737	Remote Similarity	NPD8292	Phase 2
0.6732	Remote Similarity	NPD7689	Approved
0.6727	Remote Similarity	NPD6664	Approved
0.6726	Remote Similarity	NPD6975	Discontinued
0.6725	Remote Similarity	NPD3795	Approved
0.6725	Remote Similarity	NPD3794	Approved
0.6715	Remote Similarity	NPD8279	Clinical (unspecified phase)
0.6712	Remote Similarity	NPD7944	Discontinued
0.6711	Remote Similarity	NPD7010	Phase 3
0.671	Remote Similarity	NPD6710	Phase 3
0.6698	Remote Similarity	NPD4426	Clinical (unspecified phase)
0.6697	Remote Similarity	NPD5937	Approved
0.6696	Remote Similarity	NPD1600	Suspended
0.6695	Remote Similarity	NPD5151	Clinical (unspecified phase)
0.6695	Remote Similarity	NPD7180	Phase 3
0.6682	Remote Similarity	NPD1096	Discontinued
0.6681	Remote Similarity	NPD5479	Discontinued
0.668	Remote Similarity	NPD7925	Phase 2
0.668	Remote Similarity	NPD7924	Phase 2
0.6667	Remote Similarity	NPD6733	Discontinued
0.6667	Remote Similarity	NPD6138	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD4736	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD1304	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD6803	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD3392	Approved
0.6667	Remote Similarity	NPD7809	Clinical (unspecified phase)
0.6653	Remote Similarity	NPD7269	Clinical (unspecified phase)
0.6653	Remote Similarity	NPD3986	Discontinued
0.6653	Remote Similarity	NPD7586	Clinical (unspecified phase)
0.6653	Remote Similarity	NPD6247	Clinical (unspecified phase)
0.6652	Remote Similarity	NPD2443	Approved
0.6652	Remote Similarity	NPD2879	Approved
0.6652	Remote Similarity	NPD2881	Approved
0.6652	Remote Similarity	NPD2442	Approved
0.665	Remote Similarity	NPD1631	Approved
0.664	Remote Similarity	NPD5867	Clinical (unspecified phase)
0.664	Remote Similarity	NPD4926	Clinical (unspecified phase)
0.664	Remote Similarity	NPD5532	Phase 2
0.6638	Remote Similarity	NPD6160	Clinical (unspecified phase)
0.6638	Remote Similarity	NPD5475	Discontinued
0.6637	Remote Similarity	NPD5497	Clinical (unspecified phase)
0.6635	Remote Similarity	NPD2781	Approved
0.6623	Remote Similarity	NPD2408	Discontinued
0.6622	Remote Similarity	NPD4987	Clinical (unspecified phase)
0.6622	Remote Similarity	NPD7204	Clinical (unspecified phase)
0.662	Remote Similarity	NPD5445	Approved
0.6619	Remote Similarity	NPD750	Phase 2
0.6618	Remote Similarity	NPD2780	Approved
0.6618	Remote Similarity	NPD2782	Approved
0.6611	Remote Similarity	NPD1659	Phase 1
0.6609	Remote Similarity	NPD3354	Phase 2
0.6609	Remote Similarity	NPD7069	Discontinued
0.66	Remote Similarity	NPD6724	Clinical (unspecified phase)
0.6598	Remote Similarity	NPD4850	Phase 1
0.6595	Remote Similarity	NPD8160	Phase 2
0.6593	Remote Similarity	NPD8098	Approved
0.6592	Remote Similarity	NPD3814	Phase 1
0.6592	Remote Similarity	NPD8396	Approved
0.6592	Remote Similarity	NPD3825	Phase 3
0.6592	Remote Similarity	NPD8395	Approved
0.659	Remote Similarity	NPD4988	Discontinued
0.6589	Remote Similarity	NPD7414	Clinical (unspecified phase)
0.6586	Remote Similarity	NPD6525	Clinical (unspecified phase)
0.6585	Remote Similarity	NPD2214	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