NPASS Compound

Structure

NPC258992 OpenBabel07101719522D 21 22 0 0 0 0 0 0 0 0999 V2000 -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 6.0622 -0.5000 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 -0.5000 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 3.4641 -0.0000 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 1.7321 -2.0000 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 2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -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 0.8660 -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 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 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -2.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -2.0000 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 5.1962 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 10 1 0 0 0 0 2 10 1 0 0 0 0 3 21 1 0 0 0 0 4 6 1 0 0 0 0 4 11 2 0 0 0 0 5 7 2 0 0 0 0 5 11 1 0 0 0 0 6 12 2 0 0 0 0 7 12 1 0 0 0 0 8 10 1 0 0 0 0 8 13 2 0 0 0 0 9 11 1 0 0 0 0 9 14 2 0 0 0 0 12 21 1 0 0 0 0 13 15 1 0 0 0 0 13 17 1 0 0 0 0 14 16 1 0 0 0 0 14 18 1 0 0 0 0 15 18 2 0 0 0 0 15 19 1 0 0 0 0 16 17 2 0 0 0 0 16 20 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	286.13
Volume:	298.088
LogP:	2.71
LogD:	2.931
LogS:	-3.69
# Rotatable Bonds:	3
TPSA:	74.95
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	2
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.854
Synthetic Accessibility Score:	2.717
Fsp3:	0.25
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:	-4.964
MDCK Permeability:	1.2539919225673657e-05
Pgp-inhibitor:	0.096
Pgp-substrate:	0.017
Human Intestinal Absorption (HIA):	0.341
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.891

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.06
Plasma Protein Binding (PPB):	97.30087280273438%
Volume Distribution (VD):	0.305
Pgp-substrate:	1.3967370986938477%

ADMET: Metabolism

CYP1A2-inhibitor:	0.867
CYP1A2-substrate:	0.952
CYP2C19-inhibitor:	0.522
CYP2C19-substrate:	0.065
CYP2C9-inhibitor:	0.359
CYP2C9-substrate:	0.594
CYP2D6-inhibitor:	0.034
CYP2D6-substrate:	0.135
CYP3A4-inhibitor:	0.619
CYP3A4-substrate:	0.444

ADMET: Excretion

Clearance (CL):	7.042
Half-life (T1/2):	0.676

ADMET: Toxicity

hERG Blockers:	0.021
Human Hepatotoxicity (H-HT):	0.722
Drug-inuced Liver Injury (DILI):	0.992
AMES Toxicity:	0.062
Rat Oral Acute Toxicity:	0.276
Maximum Recommended Daily Dose:	0.011
Skin Sensitization:	0.101
Carcinogencity:	0.603
Eye Corrosion:	0.004
Eye Irritation:	0.785
Respiratory Toxicity:	0.939

Download Data

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

Natural Product: NPC258992

Natural Product ID:	NPC258992
*Common Name:**	(2E/5Z)-2-[(4-Methoxyphenyl)Methylene]-5-(2-Methylpropylidene)-3,6-Piperazinedione
IUPAC Name:	(3E,6Z)-3-[(4-methoxyphenyl)methylidene]-6-(2-methylpropylidene)piperazine-2,5-dione
Synonyms:
Standard InCHIKey:	YRVUIYSTPTWLCY-NBPWYHHBSA-N
Standard InCHI:	InChI=1S/C16H18N2O3/c1-10(2)8-13-15(19)18-14(16(20)17-13)9-11-4-6-12(21-3)7-5-11/h4-10H,1-3H3,(H,17,20)(H,18,19)/b13-8-,14-9+
SMILES:	CC(C)/C=c1/c(n/c(=C/c2ccc(cc2)OC)/c(n1)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1215877
PubChem CID:	6382815
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002341] Phenol ethers [CHEMONTID:0000138] Anisoles

*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
NPO20721	Halichondria panicea	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	PMID[20695474]
NPO20721	Halichondria panicea	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	PMID[27035556]
NPO20721	Halichondria panicea	Species	Halichondriidae	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
Others	2

Activity Type	# Activity
Cell Line	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT886	Cell Line	NIH3T3	Mus musculus	Activity	=	64.0	%	PMID[502304]
NPT65	Cell Line	HepG2	Homo sapiens	Activity	=	44.0	%	PMID[502304]

☑ 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 NPC258992 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	301
0.1-0.2	3235
0.2-0.3	12893
0.3-0.4	4153
0.4-0.5	15060
0.5-0.6	6686
0.6-0.7	358
0.7-0.8	8
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.886	High Similarity	NPC303370
0.8839	High Similarity	NPC166837
0.8707	High Similarity	NPC323948
0.8644	High Similarity	NPC41801
0.8559	High Similarity	NPC256369
0.8417	Intermediate Similarity	NPC83279
0.8407	Intermediate Similarity	NPC146530
0.8268	Intermediate Similarity	NPC471953
0.825	Intermediate Similarity	NPC43275
0.8182	Intermediate Similarity	NPC263835
0.8065	Intermediate Similarity	NPC211218
0.8	Intermediate Similarity	NPC62101
0.8	Intermediate Similarity	NPC29650
0.8	Intermediate Similarity	NPC95733
0.7965	Intermediate Similarity	NPC192596
0.7939	Intermediate Similarity	NPC138365
0.7937	Intermediate Similarity	NPC29477
0.7931	Intermediate Similarity	NPC201959
0.7931	Intermediate Similarity	NPC309982
0.7917	Intermediate Similarity	NPC37302
0.7913	Intermediate Similarity	NPC113457
0.7876	Intermediate Similarity	NPC51633
0.7846	Intermediate Similarity	NPC274732
0.7833	Intermediate Similarity	NPC118202
0.7818	Intermediate Similarity	NPC471581
0.7812	Intermediate Similarity	NPC186898
0.781	Intermediate Similarity	NPC9373
0.7795	Intermediate Similarity	NPC246133
0.7795	Intermediate Similarity	NPC207541
0.7795	Intermediate Similarity	NPC71105
0.7795	Intermediate Similarity	NPC152186
0.7795	Intermediate Similarity	NPC170583
0.7795	Intermediate Similarity	NPC182147
0.7778	Intermediate Similarity	NPC177844
0.7778	Intermediate Similarity	NPC8002
0.7778	Intermediate Similarity	NPC99886
0.7778	Intermediate Similarity	NPC259134
0.7739	Intermediate Similarity	NPC474603
0.7739	Intermediate Similarity	NPC12987
0.7734	Intermediate Similarity	NPC301713
0.7734	Intermediate Similarity	NPC156944
0.7734	Intermediate Similarity	NPC251466
0.7717	Intermediate Similarity	NPC300955
0.7706	Intermediate Similarity	NPC71853
0.7699	Intermediate Similarity	NPC100870
0.7674	Intermediate Similarity	NPC157740
0.7674	Intermediate Similarity	NPC251571
0.7674	Intermediate Similarity	NPC99798
0.7674	Intermediate Similarity	NPC41331
0.7674	Intermediate Similarity	NPC291449
0.7672	Intermediate Similarity	NPC470393
0.7652	Intermediate Similarity	NPC305205
0.7636	Intermediate Similarity	NPC321956
0.7627	Intermediate Similarity	NPC75440
0.7615	Intermediate Similarity	NPC246974
0.7615	Intermediate Similarity	NPC147247
0.7615	Intermediate Similarity	NPC155838
0.76	Intermediate Similarity	NPC321133
0.7594	Intermediate Similarity	NPC303993
0.7586	Intermediate Similarity	NPC108875
0.7586	Intermediate Similarity	NPC2518
0.7586	Intermediate Similarity	NPC38079
0.7574	Intermediate Similarity	NPC83289
0.7574	Intermediate Similarity	NPC189724
0.7574	Intermediate Similarity	NPC212850
0.7563	Intermediate Similarity	NPC474272
0.7561	Intermediate Similarity	NPC82963
0.7557	Intermediate Similarity	NPC195749
0.7557	Intermediate Similarity	NPC35961
0.7557	Intermediate Similarity	NPC470706
0.7557	Intermediate Similarity	NPC52029
0.7544	Intermediate Similarity	NPC471576
0.7542	Intermediate Similarity	NPC142297
0.7538	Intermediate Similarity	NPC153990
0.75	Intermediate Similarity	NPC38458
0.75	Intermediate Similarity	NPC311737
0.748	Intermediate Similarity	NPC317254
0.7479	Intermediate Similarity	NPC96224
0.7479	Intermediate Similarity	NPC24101
0.746	Intermediate Similarity	NPC289330
0.746	Intermediate Similarity	NPC53596
0.746	Intermediate Similarity	NPC471308
0.746	Intermediate Similarity	NPC17388
0.746	Intermediate Similarity	NPC160120
0.7459	Intermediate Similarity	NPC141003
0.7459	Intermediate Similarity	NPC35344
0.7458	Intermediate Similarity	NPC231705
0.7458	Intermediate Similarity	NPC326447
0.7456	Intermediate Similarity	NPC175298
0.7444	Intermediate Similarity	NPC214869
0.7436	Intermediate Similarity	NPC109637
0.7426	Intermediate Similarity	NPC213471
0.7422	Intermediate Similarity	NPC471314
0.7422	Intermediate Similarity	NPC471315
0.7414	Intermediate Similarity	NPC300166
0.7407	Intermediate Similarity	NPC237227
0.7405	Intermediate Similarity	NPC191302
0.7402	Intermediate Similarity	NPC183262
0.7402	Intermediate Similarity	NPC473050
0.7402	Intermediate Similarity	NPC473051
0.7398	Intermediate Similarity	NPC180508
0.7398	Intermediate Similarity	NPC228287
0.7395	Intermediate Similarity	NPC227894
0.7395	Intermediate Similarity	NPC251306
0.7391	Intermediate Similarity	NPC195814
0.7388	Intermediate Similarity	NPC169766
0.7385	Intermediate Similarity	NPC476249
0.7377	Intermediate Similarity	NPC165646
0.7376	Intermediate Similarity	NPC245974
0.7373	Intermediate Similarity	NPC8302
0.7373	Intermediate Similarity	NPC42383
0.7368	Intermediate Similarity	NPC308885
0.7368	Intermediate Similarity	NPC114102
0.7368	Intermediate Similarity	NPC255550
0.7357	Intermediate Similarity	NPC247298
0.7355	Intermediate Similarity	NPC474149
0.7355	Intermediate Similarity	NPC46844
0.735	Intermediate Similarity	NPC178902
0.7348	Intermediate Similarity	NPC469977
0.7339	Intermediate Similarity	NPC185541
0.7339	Intermediate Similarity	NPC464
0.7333	Intermediate Similarity	NPC284855
0.7333	Intermediate Similarity	NPC97811
0.7333	Intermediate Similarity	NPC282477
0.7328	Intermediate Similarity	NPC13755
0.7323	Intermediate Similarity	NPC252817
0.7313	Intermediate Similarity	NPC470392
0.7304	Intermediate Similarity	NPC470161
0.7299	Intermediate Similarity	NPC14600
0.7299	Intermediate Similarity	NPC160607
0.7299	Intermediate Similarity	NPC204848
0.7299	Intermediate Similarity	NPC41473
0.7299	Intermediate Similarity	NPC312770
0.7295	Intermediate Similarity	NPC296920
0.7295	Intermediate Similarity	NPC90520
0.7295	Intermediate Similarity	NPC266932
0.7295	Intermediate Similarity	NPC55300
0.728	Intermediate Similarity	NPC19290
0.728	Intermediate Similarity	NPC85292
0.728	Intermediate Similarity	NPC229147
0.728	Intermediate Similarity	NPC54507
0.7273	Intermediate Similarity	NPC258056
0.7273	Intermediate Similarity	NPC246358
0.7273	Intermediate Similarity	NPC7097
0.7273	Intermediate Similarity	NPC36108
0.7273	Intermediate Similarity	NPC82016
0.7273	Intermediate Similarity	NPC233731
0.7265	Intermediate Similarity	NPC310905
0.7265	Intermediate Similarity	NPC12714
0.7258	Intermediate Similarity	NPC161696
0.7254	Intermediate Similarity	NPC132771
0.725	Intermediate Similarity	NPC157473
0.725	Intermediate Similarity	NPC233320
0.725	Intermediate Similarity	NPC151530
0.7246	Intermediate Similarity	NPC299583
0.7244	Intermediate Similarity	NPC281298
0.7244	Intermediate Similarity	NPC310338
0.7244	Intermediate Similarity	NPC283760
0.7236	Intermediate Similarity	NPC199462
0.7236	Intermediate Similarity	NPC474920
0.7236	Intermediate Similarity	NPC280606
0.7227	Intermediate Similarity	NPC233396
0.7227	Intermediate Similarity	NPC288760
0.7227	Intermediate Similarity	NPC154899
0.7227	Intermediate Similarity	NPC473855
0.7227	Intermediate Similarity	NPC473393
0.7227	Intermediate Similarity	NPC127676
0.7227	Intermediate Similarity	NPC227255
0.7222	Intermediate Similarity	NPC280001
0.7222	Intermediate Similarity	NPC474933
0.7217	Intermediate Similarity	NPC473388
0.7213	Intermediate Similarity	NPC475852
0.7213	Intermediate Similarity	NPC137685
0.7209	Intermediate Similarity	NPC474862
0.7206	Intermediate Similarity	NPC473463
0.7206	Intermediate Similarity	NPC218530
0.7203	Intermediate Similarity	NPC179686
0.7203	Intermediate Similarity	NPC298224
0.72	Intermediate Similarity	NPC296526
0.7197	Intermediate Similarity	NPC218323
0.7194	Intermediate Similarity	NPC477838
0.7194	Intermediate Similarity	NPC477837
0.7194	Intermediate Similarity	NPC314113
0.719	Intermediate Similarity	NPC153690
0.7188	Intermediate Similarity	NPC232316
0.7188	Intermediate Similarity	NPC227217
0.7188	Intermediate Similarity	NPC56214
0.7188	Intermediate Similarity	NPC95614
0.7188	Intermediate Similarity	NPC117780
0.7188	Intermediate Similarity	NPC165133
0.7188	Intermediate Similarity	NPC242885
0.7185	Intermediate Similarity	NPC130595
0.7185	Intermediate Similarity	NPC97870
0.7185	Intermediate Similarity	NPC307123
0.7185	Intermediate Similarity	NPC93882
0.7185	Intermediate Similarity	NPC247018
0.7179	Intermediate Similarity	NPC107101
0.7177	Intermediate Similarity	NPC165106
0.7177	Intermediate Similarity	NPC26524
0.7177	Intermediate Similarity	NPC264782

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 NPC258992 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	217
0.1-0.2	789
0.2-0.3	939
0.3-0.4	1709
0.4-0.5	3556
0.5-0.6	1798
0.6-0.7	140
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8843	High Similarity	NPD4993	Discontinued
0.8065	Intermediate Similarity	NPD3676	Clinical (unspecified phase)
0.806	Intermediate Similarity	NPD5481	Discontinued
0.7815	Intermediate Similarity	NPD821	Approved
0.7638	Intermediate Similarity	NPD3685	Discontinued
0.76	Intermediate Similarity	NPD2668	Approved
0.76	Intermediate Similarity	NPD2667	Approved
0.75	Intermediate Similarity	NPD6582	Phase 2
0.75	Intermediate Similarity	NPD1669	Approved
0.75	Intermediate Similarity	NPD6583	Phase 3
0.7479	Intermediate Similarity	NPD2684	Approved
0.7458	Intermediate Similarity	NPD3134	Approved
0.7419	Intermediate Similarity	NPD3596	Phase 2
0.7368	Intermediate Similarity	NPD3145	Approved
0.7368	Intermediate Similarity	NPD3144	Approved
0.7328	Intermediate Similarity	NPD6584	Phase 3
0.7308	Intermediate Similarity	NPD2922	Phase 1
0.7302	Intermediate Similarity	NPD6580	Approved
0.7302	Intermediate Similarity	NPD6581	Approved
0.7287	Intermediate Similarity	NPD2230	Approved
0.7287	Intermediate Similarity	NPD2233	Approved
0.7287	Intermediate Similarity	NPD2232	Approved
0.7273	Intermediate Similarity	NPD5451	Approved
0.7266	Intermediate Similarity	NPD3421	Phase 3
0.7266	Intermediate Similarity	NPD3847	Discontinued
0.7244	Intermediate Similarity	NPD6830	Clinical (unspecified phase)
0.7239	Intermediate Similarity	NPD5109	Approved
0.7239	Intermediate Similarity	NPD5111	Phase 2
0.7239	Intermediate Similarity	NPD5110	Phase 2
0.7236	Intermediate Similarity	NPD7843	Approved
0.7231	Intermediate Similarity	NPD4129	Approved
0.72	Intermediate Similarity	NPD709	Approved
0.72	Intermediate Similarity	NPD2557	Approved
0.7193	Intermediate Similarity	NPD2934	Approved
0.7193	Intermediate Similarity	NPD2933	Approved
0.7185	Intermediate Similarity	NPD2674	Phase 3
0.7185	Intermediate Similarity	NPD1423	Approved
0.7185	Intermediate Similarity	NPD3058	Clinical (unspecified phase)
0.7177	Intermediate Similarity	NPD5283	Phase 1
0.7167	Intermediate Similarity	NPD968	Approved
0.7164	Intermediate Similarity	NPD3165	Approved
0.7164	Intermediate Similarity	NPD3167	Approved
0.7164	Intermediate Similarity	NPD3166	Approved
0.7164	Intermediate Similarity	NPD3164	Approved
0.7154	Intermediate Similarity	NPD228	Approved
0.7153	Intermediate Similarity	NPD4097	Suspended
0.7153	Intermediate Similarity	NPD1772	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD4149	Clinical (unspecified phase)
0.7132	Intermediate Similarity	NPD5837	Clinical (unspecified phase)
0.713	Intermediate Similarity	NPD2859	Approved
0.713	Intermediate Similarity	NPD2860	Approved
0.7121	Intermediate Similarity	NPD1819	Approved
0.7121	Intermediate Similarity	NPD3568	Approved
0.7121	Intermediate Similarity	NPD1820	Approved
0.7121	Intermediate Similarity	NPD1817	Approved
0.7121	Intermediate Similarity	NPD3567	Approved
0.7121	Intermediate Similarity	NPD1818	Approved
0.7111	Intermediate Similarity	NPD1048	Approved
0.7107	Intermediate Similarity	NPD1358	Approved
0.7094	Intermediate Similarity	NPD3020	Approved
0.7068	Intermediate Similarity	NPD3690	Phase 2
0.7068	Intermediate Similarity	NPD3691	Phase 2
0.7063	Intermediate Similarity	NPD7157	Approved
0.7059	Intermediate Similarity	NPD840	Approved
0.7059	Intermediate Similarity	NPD5745	Approved
0.7059	Intermediate Similarity	NPD839	Approved
0.7059	Intermediate Similarity	NPD1726	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD7477	Discontinued
0.7055	Intermediate Similarity	NPD5267	Discontinued
0.705	Intermediate Similarity	NPD4108	Discontinued
0.7045	Intermediate Similarity	NPD7258	Clinical (unspecified phase)
0.7042	Intermediate Similarity	NPD1662	Clinical (unspecified phase)
0.7042	Intermediate Similarity	NPD6331	Phase 2
0.7037	Intermediate Similarity	NPD3179	Approved
0.7037	Intermediate Similarity	NPD3180	Approved
0.7037	Intermediate Similarity	NPD1024	Discontinued
0.7029	Intermediate Similarity	NPD3054	Approved
0.7029	Intermediate Similarity	NPD2157	Approved
0.7029	Intermediate Similarity	NPD3052	Approved
0.7023	Intermediate Similarity	NPD2231	Phase 2
0.7023	Intermediate Similarity	NPD2235	Phase 2
0.7015	Intermediate Similarity	NPD2040	Clinical (unspecified phase)
0.7015	Intermediate Similarity	NPD2407	Clinical (unspecified phase)
0.7015	Intermediate Similarity	NPD1712	Approved
0.7014	Intermediate Similarity	NPD2752	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD1725	Approved
0.7	Intermediate Similarity	NPD111	Approved
0.7	Intermediate Similarity	NPD3175	Clinical (unspecified phase)
0.6993	Remote Similarity	NPD3692	Discontinued
0.6992	Remote Similarity	NPD3827	Clinical (unspecified phase)
0.6992	Remote Similarity	NPD1232	Clinical (unspecified phase)
0.6992	Remote Similarity	NPD1770	Clinical (unspecified phase)
0.6986	Remote Similarity	NPD7131	Phase 3
0.6985	Remote Similarity	NPD3056	Clinical (unspecified phase)
0.6985	Remote Similarity	NPD1039	Discontinued
0.6984	Remote Similarity	NPD595	Approved
0.6984	Remote Similarity	NPD593	Approved
0.6977	Remote Similarity	NPD2594	Approved
0.6977	Remote Similarity	NPD2595	Approved
0.6972	Remote Similarity	NPD2459	Approved
0.6972	Remote Similarity	NPD44	Approved
0.6972	Remote Similarity	NPD2458	Approved
0.6972	Remote Similarity	NPD2460	Phase 3
0.6972	Remote Similarity	NPD6364	Approved
0.697	Remote Similarity	NPD6543	Approved
0.697	Remote Similarity	NPD6540	Phase 3
0.697	Remote Similarity	NPD3600	Clinical (unspecified phase)
0.697	Remote Similarity	NPD6539	Approved
0.697	Remote Similarity	NPD6542	Approved
0.6967	Remote Similarity	NPD290	Approved
0.6966	Remote Similarity	NPD4123	Phase 3
0.6963	Remote Similarity	NPD682	Discontinued
0.696	Remote Similarity	NPD5535	Approved
0.6953	Remote Similarity	NPD254	Approved
0.6947	Remote Similarity	NPD776	Approved
0.6934	Remote Similarity	NPD7265	Discontinued
0.6929	Remote Similarity	NPD6671	Approved
0.6929	Remote Similarity	NPD6387	Discontinued
0.6923	Remote Similarity	NPD6658	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD4626	Approved
0.6923	Remote Similarity	NPD2423	Clinical (unspecified phase)
0.6918	Remote Similarity	NPD4186	Clinical (unspecified phase)
0.6917	Remote Similarity	NPD6538	Approved
0.6917	Remote Similarity	NPD6541	Approved
0.6913	Remote Similarity	NPD980	Clinical (unspecified phase)
0.6912	Remote Similarity	NPD5746	Approved
0.6912	Remote Similarity	NPD6179	Discontinued
0.6912	Remote Similarity	NPD5163	Phase 2
0.6906	Remote Similarity	NPD4579	Clinical (unspecified phase)
0.6905	Remote Similarity	NPD2234	Approved
0.6905	Remote Similarity	NPD592	Approved
0.6905	Remote Similarity	NPD594	Approved
0.6905	Remote Similarity	NPD2229	Approved
0.6905	Remote Similarity	NPD2228	Approved
0.6903	Remote Similarity	NPD9295	Approved
0.6901	Remote Similarity	NPD1044	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD7153	Discontinued
0.6901	Remote Similarity	NPD3655	Clinical (unspecified phase)
0.6899	Remote Similarity	NPD1548	Phase 1
0.6899	Remote Similarity	NPD1182	Approved
0.6884	Remote Similarity	NPD2238	Phase 2
0.6879	Remote Similarity	NPD2161	Phase 2
0.6871	Remote Similarity	NPD2122	Discontinued
0.6866	Remote Similarity	NPD1794	Approved
0.6857	Remote Similarity	NPD696	Discontinued
0.6853	Remote Similarity	NPD5289	Phase 2
0.6846	Remote Similarity	NPD3049	Approved
0.6846	Remote Similarity	NPD3443	Approved
0.6846	Remote Similarity	NPD3445	Approved
0.6846	Remote Similarity	NPD6382	Discontinued
0.6846	Remote Similarity	NPD3444	Approved
0.6846	Remote Similarity	NPD5617	Suspended
0.6846	Remote Similarity	NPD1357	Approved
0.6842	Remote Similarity	NPD2428	Approved
0.6842	Remote Similarity	NPD2429	Approved
0.6842	Remote Similarity	NPD4379	Clinical (unspecified phase)
0.6835	Remote Similarity	NPD654	Phase 3
0.6831	Remote Similarity	NPD7083	Clinical (unspecified phase)
0.6828	Remote Similarity	NPD3281	Clinical (unspecified phase)
0.6822	Remote Similarity	NPD5536	Phase 2
0.6815	Remote Similarity	NPD7451	Discontinued
0.6815	Remote Similarity	NPD7018	Phase 2
0.6812	Remote Similarity	NPD3162	Approved
0.6812	Remote Similarity	NPD3163	Approved
0.6809	Remote Similarity	NPD3846	Clinical (unspecified phase)
0.6809	Remote Similarity	NPD6380	Phase 1
0.6803	Remote Similarity	NPD7526	Approved
0.6803	Remote Similarity	NPD52	Approved
0.6803	Remote Similarity	NPD7527	Clinical (unspecified phase)
0.6803	Remote Similarity	NPD6390	Discontinued
0.68	Remote Similarity	NPD2541	Clinical (unspecified phase)
0.68	Remote Similarity	NPD3778	Approved
0.6794	Remote Similarity	NPD2554	Approved
0.6794	Remote Similarity	NPD5846	Approved
0.6794	Remote Similarity	NPD6516	Phase 2
0.6794	Remote Similarity	NPD2556	Approved
0.6791	Remote Similarity	NPD196	Phase 1
0.6788	Remote Similarity	NPD3136	Phase 2
0.6783	Remote Similarity	NPD7596	Clinical (unspecified phase)
0.6781	Remote Similarity	NPD4357	Discontinued
0.6779	Remote Similarity	NPD4005	Discontinued
0.6776	Remote Similarity	NPD3560	Approved
0.6776	Remote Similarity	NPD3557	Approved
0.6776	Remote Similarity	NPD3559	Clinical (unspecified phase)
0.6776	Remote Similarity	NPD3558	Approved
0.6776	Remote Similarity	NPD3556	Approved
0.6772	Remote Similarity	NPD1241	Discontinued
0.6769	Remote Similarity	NPD2486	Discontinued
0.6767	Remote Similarity	NPD1840	Phase 2
0.6763	Remote Similarity	NPD3597	Clinical (unspecified phase)
0.6763	Remote Similarity	NPD1558	Phase 1
0.6759	Remote Similarity	NPD2219	Phase 1
0.6752	Remote Similarity	NPD1432	Clinical (unspecified phase)
0.6741	Remote Similarity	NPD4098	Discontinued
0.6739	Remote Similarity	NPD7294	Phase 1
0.6739	Remote Similarity	NPD5718	Phase 2
0.6739	Remote Similarity	NPD3374	Clinical (unspecified phase)
0.6735	Remote Similarity	NPD5348	Clinical (unspecified phase)
0.6735	Remote Similarity	NPD4739	Approved
0.6735	Remote Similarity	NPD3985	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