NPASS Compound

Structure

NPC211218 OpenBabel07101718192D 23 24 0 0 1 0 0 0 0 0999 V2000 -1.7321 -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 9.5263 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6603 3.0000 0.0000 C 0 0 0 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 7.7942 2.5000 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 6.9282 1.0000 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 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 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 1.5000 0.0000 C 0 0 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 7.7942 1.5000 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 0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1962 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 1.5000 0.0000 N 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 -0.8660 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 2.5000 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 7 2 0 0 0 0 6 15 2 0 0 0 0 7 15 1 0 0 0 0 8 13 2 0 0 0 0 8 15 1 0 0 0 0 9 11 1 0 0 0 0 9 16 2 0 0 0 0 10 12 2 0 0 0 0 10 16 1 0 0 0 0 11 17 2 0 0 0 0 12 17 1 0 0 0 0 13 19 1 0 0 0 0 14 20 1 0 0 0 0 16 18 1 0 0 0 0 17 22 1 0 0 0 0 18 14 1 6 0 0 0 18 23 1 0 0 0 0 19 20 2 3 0 0 0 19 21 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	311.15
Volume:	336.343
LogP:	2.912
LogD:	3.278
LogS:	-4.248
# Rotatable Bonds:	8
TPSA:	47.56
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.799
Synthetic Accessibility Score:	2.44
Fsp3:	0.211
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:	-4.739
MDCK Permeability:	1.5067409549374133e-05
Pgp-inhibitor:	0.964
Pgp-substrate:	0.009
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.018
30% Bioavailability (F30%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.525
Plasma Protein Binding (PPB):	95.07355499267578%
Volume Distribution (VD):	0.783
Pgp-substrate:	2.0781962871551514%

ADMET: Metabolism

CYP1A2-inhibitor:	0.817
CYP1A2-substrate:	0.487
CYP2C19-inhibitor:	0.873
CYP2C19-substrate:	0.777
CYP2C9-inhibitor:	0.671
CYP2C9-substrate:	0.81
CYP2D6-inhibitor:	0.295
CYP2D6-substrate:	0.899
CYP3A4-inhibitor:	0.676
CYP3A4-substrate:	0.294

ADMET: Excretion

Clearance (CL):	7.731
Half-life (T1/2):	0.183

ADMET: Toxicity

hERG Blockers:	0.829
Human Hepatotoxicity (H-HT):	0.564
Drug-inuced Liver Injury (DILI):	0.562
AMES Toxicity:	0.935
Rat Oral Acute Toxicity:	0.038
Maximum Recommended Daily Dose:	0.184
Skin Sensitization:	0.841
Carcinogencity:	0.283
Eye Corrosion:	0.017
Eye Irritation:	0.592
Respiratory Toxicity:	0.621

Download Data

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

Natural Product: NPC211218

Natural Product ID:	NPC211218
*Common Name:**	(-)-O-Methylether Aegeline
IUPAC Name:	(E)-N-[(2S)-2-methoxy-2-(4-methoxyphenyl)ethyl]-3-phenylprop-2-enamide
Synonyms:
Standard InCHIKey:	PJIOBHFHQZPYOX-INMULRNOSA-N
Standard InCHI:	InChI=1S/C19H21NO3/c1-22-17-11-9-16(10-12-17)18(23-2)14-20-19(21)13-8-15-6-4-3-5-7-15/h3-13,18H,14H2,1-2H3,(H,20,21)/b13-8+/t18-/m1/s1
SMILES:	CO[C@@H](c1ccc(cc1)OC)CN=C(/C=C/c1ccccc1)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL444650
PubChem CID:	11209134
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0002810] Cinnamic acid amides

*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
NPO5045	Aegle marmelos	Species	Rutaceae	Eukaryota	leaves	n.a.	n.a.	PMID[18760601]
NPO5045	Aegle marmelos	Species	Rutaceae	Eukaryota	n.a.	bark	n.a.	PMID[21875114]
NPO5045	Aegle marmelos	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23434131]
NPO5045	Aegle marmelos	Species	Rutaceae	Eukaryota	n.a.	fruit	n.a.	PMID[26247834]
NPO5045	Aegle marmelos	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30579794]
NPO5045	Aegle marmelos	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5045	Aegle marmelos	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5045	Aegle marmelos	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

☑ 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	1

Activity Type	# Activity
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified		Inhibition	=	12.6	%	PMID[467822]

☑ 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 NPC211218 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	161
0.1-0.2	1310
0.2-0.3	7038
0.3-0.4	11057
0.4-0.5	5743
0.5-0.6	11369
0.6-0.7	5321
0.7-0.8	650
0.8-0.85	33
0.85-0.9	9
0.9-0.95	3
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9746	High Similarity	NPC62101
0.9746	High Similarity	NPC95733
0.95	High Similarity	NPC29477
0.916	High Similarity	NPC263835
0.9076	High Similarity	NPC43275
0.8923	High Similarity	NPC299583
0.8739	High Similarity	NPC303370
0.8718	High Similarity	NPC166837
0.8702	High Similarity	NPC160607
0.8702	High Similarity	NPC14600
0.8702	High Similarity	NPC204848
0.8702	High Similarity	NPC41473
0.8702	High Similarity	NPC312770
0.8657	High Similarity	NPC178466
0.8657	High Similarity	NPC63628
0.8651	High Similarity	NPC301713
0.8607	High Similarity	NPC256369
0.8438	Intermediate Similarity	NPC251571
0.8372	Intermediate Similarity	NPC155838
0.8333	Intermediate Similarity	NPC471314
0.8333	Intermediate Similarity	NPC471315
0.8321	Intermediate Similarity	NPC471953
0.8321	Intermediate Similarity	NPC214869
0.8308	Intermediate Similarity	NPC35961
0.8308	Intermediate Similarity	NPC52029
0.8308	Intermediate Similarity	NPC195749
0.8305	Intermediate Similarity	NPC24101
0.8305	Intermediate Similarity	NPC96224
0.8286	Intermediate Similarity	NPC182119
0.8273	Intermediate Similarity	NPC115144
0.8273	Intermediate Similarity	NPC277857
0.8244	Intermediate Similarity	NPC114102
0.8222	Intermediate Similarity	NPC296898
0.8175	Intermediate Similarity	NPC83279
0.8162	Intermediate Similarity	NPC189724
0.8162	Intermediate Similarity	NPC83289
0.8162	Intermediate Similarity	NPC212850
0.8154	Intermediate Similarity	NPC153990
0.8129	Intermediate Similarity	NPC313414
0.8095	Intermediate Similarity	NPC321133
0.8095	Intermediate Similarity	NPC289330
0.8095	Intermediate Similarity	NPC160120
0.8095	Intermediate Similarity	NPC17388
0.8095	Intermediate Similarity	NPC53596
0.8095	Intermediate Similarity	NPC471308
0.8085	Intermediate Similarity	NPC471032
0.8085	Intermediate Similarity	NPC470935
0.8067	Intermediate Similarity	NPC142297
0.8065	Intermediate Similarity	NPC258992
0.8015	Intermediate Similarity	NPC186898
0.8015	Intermediate Similarity	NPC254610
0.8	Intermediate Similarity	NPC153690
0.7983	Intermediate Similarity	NPC113457
0.7983	Intermediate Similarity	NPC231705
0.7943	Intermediate Similarity	NPC132771
0.7943	Intermediate Similarity	NPC245974
0.7934	Intermediate Similarity	NPC258056
0.7934	Intermediate Similarity	NPC474272
0.7929	Intermediate Similarity	NPC247298
0.792	Intermediate Similarity	NPC82963
0.7917	Intermediate Similarity	NPC251306
0.791	Intermediate Similarity	NPC470392
0.7902	Intermediate Similarity	NPC114659
0.7902	Intermediate Similarity	NPC139699
0.7881	Intermediate Similarity	NPC178902
0.7881	Intermediate Similarity	NPC305205
0.7872	Intermediate Similarity	NPC5462
0.7869	Intermediate Similarity	NPC474149
0.7857	Intermediate Similarity	NPC38458
0.7857	Intermediate Similarity	NPC323948
0.7857	Intermediate Similarity	NPC311737
0.7851	Intermediate Similarity	NPC146530
0.784	Intermediate Similarity	NPC185541
0.784	Intermediate Similarity	NPC464
0.7812	Intermediate Similarity	NPC41801
0.7803	Intermediate Similarity	NPC218323
0.7787	Intermediate Similarity	NPC265211
0.7787	Intermediate Similarity	NPC306045
0.7778	Intermediate Similarity	NPC229147
0.7778	Intermediate Similarity	NPC54507
0.7778	Intermediate Similarity	NPC85292
0.7778	Intermediate Similarity	NPC93882
0.7778	Intermediate Similarity	NPC130595
0.7761	Intermediate Similarity	NPC470706
0.776	Intermediate Similarity	NPC118202
0.775	Intermediate Similarity	NPC42383
0.7744	Intermediate Similarity	NPC99798
0.7744	Intermediate Similarity	NPC157740
0.773	Intermediate Similarity	NPC78530
0.7721	Intermediate Similarity	NPC285078
0.7721	Intermediate Similarity	NPC6854
0.7721	Intermediate Similarity	NPC313737
0.7717	Intermediate Similarity	NPC283468
0.7717	Intermediate Similarity	NPC474933
0.7714	Intermediate Similarity	NPC195814
0.7714	Intermediate Similarity	NPC474128
0.771	Intermediate Similarity	NPC328267
0.771	Intermediate Similarity	NPC307020
0.7705	Intermediate Similarity	NPC75440
0.7705	Intermediate Similarity	NPC309982
0.7705	Intermediate Similarity	NPC201959
0.7705	Intermediate Similarity	NPC97811
0.7698	Intermediate Similarity	NPC37302
0.7698	Intermediate Similarity	NPC317254
0.7692	Intermediate Similarity	NPC474862
0.7687	Intermediate Similarity	NPC10221
0.7687	Intermediate Similarity	NPC187028
0.7687	Intermediate Similarity	NPC18249
0.7687	Intermediate Similarity	NPC140915
0.7687	Intermediate Similarity	NPC147247
0.7687	Intermediate Similarity	NPC246974
0.7687	Intermediate Similarity	NPC305700
0.7687	Intermediate Similarity	NPC197741
0.768	Intermediate Similarity	NPC123175
0.768	Intermediate Similarity	NPC176730
0.768	Intermediate Similarity	NPC26524
0.7671	Intermediate Similarity	NPC127402
0.7669	Intermediate Similarity	NPC156944
0.7669	Intermediate Similarity	NPC251466
0.7664	Intermediate Similarity	NPC218530
0.7656	Intermediate Similarity	NPC131118
0.7656	Intermediate Similarity	NPC122009
0.7647	Intermediate Similarity	NPC274732
0.7642	Intermediate Similarity	NPC290566
0.7642	Intermediate Similarity	NPC145638
0.7638	Intermediate Similarity	NPC141090
0.7634	Intermediate Similarity	NPC100099
0.7634	Intermediate Similarity	NPC36016
0.7634	Intermediate Similarity	NPC150026
0.7627	Intermediate Similarity	NPC100870
0.7619	Intermediate Similarity	NPC228287
0.7619	Intermediate Similarity	NPC180508
0.7612	Intermediate Similarity	NPC41331
0.7612	Intermediate Similarity	NPC291449
0.7606	Intermediate Similarity	NPC135349
0.7603	Intermediate Similarity	NPC470393
0.7603	Intermediate Similarity	NPC8302
0.7603	Intermediate Similarity	NPC154899
0.7603	Intermediate Similarity	NPC233396
0.76	Intermediate Similarity	NPC290353
0.76	Intermediate Similarity	NPC153795
0.76	Intermediate Similarity	NPC42911
0.7597	Intermediate Similarity	NPC268572
0.7594	Intermediate Similarity	NPC170583
0.7594	Intermediate Similarity	NPC152186
0.7594	Intermediate Similarity	NPC246133
0.7594	Intermediate Similarity	NPC182147
0.7594	Intermediate Similarity	NPC71105
0.7594	Intermediate Similarity	NPC207541
0.7583	Intermediate Similarity	NPC192596
0.7576	Intermediate Similarity	NPC76465
0.7576	Intermediate Similarity	NPC255253
0.7576	Intermediate Similarity	NPC471693
0.7576	Intermediate Similarity	NPC38761
0.7574	Intermediate Similarity	NPC326599
0.7574	Intermediate Similarity	NPC329595
0.7574	Intermediate Similarity	NPC45191
0.7574	Intermediate Similarity	NPC255550
0.7574	Intermediate Similarity	NPC308885
0.7568	Intermediate Similarity	NPC56635
0.7568	Intermediate Similarity	NPC212699
0.7568	Intermediate Similarity	NPC207675
0.7559	Intermediate Similarity	NPC10286
0.7559	Intermediate Similarity	NPC53906
0.7559	Intermediate Similarity	NPC213
0.7541	Intermediate Similarity	NPC92623
0.7541	Intermediate Similarity	NPC135464
0.754	Intermediate Similarity	NPC141003
0.754	Intermediate Similarity	NPC35344
0.7535	Intermediate Similarity	NPC222039
0.7535	Intermediate Similarity	NPC100478
0.7521	Intermediate Similarity	NPC12987
0.7521	Intermediate Similarity	NPC108875
0.7521	Intermediate Similarity	NPC38079
0.7521	Intermediate Similarity	NPC474603
0.7519	Intermediate Similarity	NPC106914
0.7519	Intermediate Similarity	NPC86502
0.7519	Intermediate Similarity	NPC197351
0.7519	Intermediate Similarity	NPC94276
0.7519	Intermediate Similarity	NPC246648
0.7519	Intermediate Similarity	NPC300955
0.7519	Intermediate Similarity	NPC109822
0.7519	Intermediate Similarity	NPC134195
0.7518	Intermediate Similarity	NPC314113
0.7518	Intermediate Similarity	NPC477837
0.7518	Intermediate Similarity	NPC477838
0.7517	Intermediate Similarity	NPC107602
0.75	Intermediate Similarity	NPC50380
0.75	Intermediate Similarity	NPC71090
0.75	Intermediate Similarity	NPC275027
0.75	Intermediate Similarity	NPC51633
0.75	Intermediate Similarity	NPC179250
0.75	Intermediate Similarity	NPC471316
0.75	Intermediate Similarity	NPC300166
0.75	Intermediate Similarity	NPC82016
0.75	Intermediate Similarity	NPC9373
0.7481	Intermediate Similarity	NPC284078
0.7481	Intermediate Similarity	NPC183262
0.7481	Intermediate Similarity	NPC318357
0.7481	Intermediate Similarity	NPC191302

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 NPC211218 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	125
0.1-0.2	706
0.2-0.3	1100
0.3-0.4	1899
0.4-0.5	2574
0.5-0.6	1739
0.6-0.7	808
0.7-0.8	195
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
0.8413	Intermediate Similarity	NPD1669	Approved
0.8271	Intermediate Similarity	NPD3054	Approved
0.8271	Intermediate Similarity	NPD3052	Approved
0.8268	Intermediate Similarity	NPD3676	Clinical (unspecified phase)
0.8154	Intermediate Similarity	NPD4993	Discontinued
0.8125	Intermediate Similarity	NPD6582	Phase 2
0.8125	Intermediate Similarity	NPD6583	Phase 3
0.8095	Intermediate Similarity	NPD2667	Approved
0.8095	Intermediate Similarity	NPD2668	Approved
0.8065	Intermediate Similarity	NPD3596	Phase 2
0.8014	Intermediate Similarity	NPD4123	Phase 3
0.7984	Intermediate Similarity	NPD3685	Discontinued
0.797	Intermediate Similarity	NPD3056	Clinical (unspecified phase)
0.7939	Intermediate Similarity	NPD6584	Phase 3
0.7937	Intermediate Similarity	NPD6580	Approved
0.7937	Intermediate Similarity	NPD6581	Approved
0.791	Intermediate Similarity	NPD7477	Discontinued
0.7886	Intermediate Similarity	NPD821	Approved
0.7874	Intermediate Similarity	NPD6830	Clinical (unspecified phase)
0.7868	Intermediate Similarity	NPD1772	Clinical (unspecified phase)
0.784	Intermediate Similarity	NPD2557	Approved
0.7832	Intermediate Similarity	NPD5261	Clinical (unspecified phase)
0.7786	Intermediate Similarity	NPD7258	Clinical (unspecified phase)
0.7786	Intermediate Similarity	NPD3060	Approved
0.7778	Intermediate Similarity	NPD840	Approved
0.7778	Intermediate Similarity	NPD839	Approved
0.7778	Intermediate Similarity	NPD2674	Phase 3
0.7769	Intermediate Similarity	NPD2561	Approved
0.7769	Intermediate Similarity	NPD2562	Approved
0.774	Intermediate Similarity	NPD4675	Approved
0.774	Intermediate Similarity	NPD4678	Approved
0.7734	Intermediate Similarity	NPD2594	Approved
0.7734	Intermediate Similarity	NPD2595	Approved
0.773	Intermediate Similarity	NPD6331	Phase 2
0.7721	Intermediate Similarity	NPD2238	Phase 2
0.7721	Intermediate Similarity	NPD5837	Clinical (unspecified phase)
0.771	Intermediate Similarity	NPD2428	Approved
0.771	Intermediate Similarity	NPD2429	Approved
0.771	Intermediate Similarity	NPD4659	Approved
0.7692	Intermediate Similarity	NPD7212	Phase 2
0.7692	Intermediate Similarity	NPD7213	Phase 3
0.7674	Intermediate Similarity	NPD2556	Approved
0.7674	Intermediate Similarity	NPD2554	Approved
0.7674	Intermediate Similarity	NPD5238	Clinical (unspecified phase)
0.766	Intermediate Similarity	NPD4236	Phase 3
0.766	Intermediate Similarity	NPD4237	Approved
0.7655	Intermediate Similarity	NPD7131	Phase 3
0.7643	Intermediate Similarity	NPD1375	Discontinued
0.7642	Intermediate Similarity	NPD9380	Clinical (unspecified phase)
0.7634	Intermediate Similarity	NPD2230	Approved
0.7634	Intermediate Similarity	NPD2231	Phase 2
0.7634	Intermediate Similarity	NPD2232	Approved
0.7634	Intermediate Similarity	NPD2233	Approved
0.7634	Intermediate Similarity	NPD2235	Phase 2
0.763	Intermediate Similarity	NPD1024	Discontinued
0.7626	Intermediate Similarity	NPD4108	Discontinued
0.7606	Intermediate Similarity	NPD6658	Clinical (unspecified phase)
0.7594	Intermediate Similarity	NPD4103	Phase 2
0.7594	Intermediate Similarity	NPD3567	Approved
0.7594	Intermediate Similarity	NPD3568	Approved
0.7594	Intermediate Similarity	NPD4104	Clinical (unspecified phase)
0.7589	Intermediate Similarity	NPD7596	Clinical (unspecified phase)
0.7589	Intermediate Similarity	NPD7153	Discontinued
0.7578	Intermediate Similarity	NPD856	Approved
0.7578	Intermediate Similarity	NPD16	Approved
0.7576	Intermediate Similarity	NPD6539	Approved
0.7576	Intermediate Similarity	NPD6542	Approved
0.7576	Intermediate Similarity	NPD6540	Phase 3
0.7576	Intermediate Similarity	NPD6543	Approved
0.7574	Intermediate Similarity	NPD3374	Clinical (unspecified phase)
0.7574	Intermediate Similarity	NPD3145	Approved
0.7574	Intermediate Similarity	NPD3144	Approved
0.7571	Intermediate Similarity	NPD2161	Phase 2
0.7568	Intermediate Similarity	NPD6072	Discontinued
0.7556	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7551	Intermediate Similarity	NPD4005	Discontinued
0.755	Intermediate Similarity	NPD7975	Clinical (unspecified phase)
0.7537	Intermediate Similarity	NPD7018	Phase 2
0.7535	Intermediate Similarity	NPD2460	Phase 3
0.7535	Intermediate Similarity	NPD2459	Approved
0.7535	Intermediate Similarity	NPD2458	Approved
0.7535	Intermediate Similarity	NPD2976	Clinical (unspecified phase)
0.7519	Intermediate Similarity	NPD6541	Approved
0.7519	Intermediate Similarity	NPD2486	Discontinued
0.7519	Intermediate Similarity	NPD6538	Approved
0.7517	Intermediate Similarity	NPD7447	Phase 1
0.7517	Intermediate Similarity	NPD3536	Discontinued
0.75	Intermediate Similarity	NPD3179	Approved
0.75	Intermediate Similarity	NPD3180	Approved
0.75	Intermediate Similarity	NPD6179	Discontinued
0.7482	Intermediate Similarity	NPD2157	Approved
0.7481	Intermediate Similarity	NPD3421	Phase 3
0.7481	Intermediate Similarity	NPD1712	Approved
0.7467	Intermediate Similarity	NPD5772	Approved
0.7467	Intermediate Similarity	NPD5773	Approved
0.7462	Intermediate Similarity	NPD6382	Discontinued
0.7462	Intermediate Similarity	NPD3049	Approved
0.7445	Intermediate Similarity	NPD1048	Approved
0.7444	Intermediate Similarity	NPD4129	Approved
0.7442	Intermediate Similarity	NPD317	Approved
0.7442	Intermediate Similarity	NPD318	Approved
0.7431	Intermediate Similarity	NPD3692	Discontinued
0.7431	Intermediate Similarity	NPD5241	Discontinued
0.7429	Intermediate Similarity	NPD3555	Approved
0.7429	Intermediate Similarity	NPD3554	Approved
0.7429	Intermediate Similarity	NPD3553	Approved
0.7429	Intermediate Similarity	NPD3552	Approved
0.7422	Intermediate Similarity	NPD709	Approved
0.7419	Intermediate Similarity	NPD2684	Approved
0.7413	Intermediate Similarity	NPD4162	Approved
0.7407	Intermediate Similarity	NPD7451	Discontinued
0.7402	Intermediate Similarity	NPD2229	Approved
0.7402	Intermediate Similarity	NPD2228	Approved
0.7402	Intermediate Similarity	NPD2234	Approved
0.7394	Intermediate Similarity	NPD2029	Clinical (unspecified phase)
0.7394	Intermediate Similarity	NPD5865	Clinical (unspecified phase)
0.7391	Intermediate Similarity	NPD3532	Approved
0.7391	Intermediate Similarity	NPD5745	Approved
0.7391	Intermediate Similarity	NPD3058	Clinical (unspecified phase)
0.7391	Intermediate Similarity	NPD7265	Discontinued
0.7391	Intermediate Similarity	NPD1423	Approved
0.7391	Intermediate Similarity	NPD3530	Approved
0.7391	Intermediate Similarity	NPD3531	Approved
0.7388	Intermediate Similarity	NPD2922	Phase 1
0.7385	Intermediate Similarity	NPD1548	Phase 1
0.7379	Intermediate Similarity	NPD6667	Approved
0.7379	Intermediate Similarity	NPD6815	Approved
0.7379	Intermediate Similarity	NPD6666	Approved
0.7372	Intermediate Similarity	NPD5163	Phase 2
0.736	Intermediate Similarity	NPD5451	Approved
0.7357	Intermediate Similarity	NPD4579	Clinical (unspecified phase)
0.7348	Intermediate Similarity	NPD3294	Phase 2
0.7348	Intermediate Similarity	NPD3847	Discontinued
0.7344	Intermediate Similarity	NPD593	Approved
0.7344	Intermediate Similarity	NPD595	Approved
0.7333	Intermediate Similarity	NPD4098	Discontinued
0.7333	Intermediate Similarity	NPD1820	Approved
0.7333	Intermediate Similarity	NPD1818	Approved
0.7333	Intermediate Similarity	NPD1819	Approved
0.7333	Intermediate Similarity	NPD1817	Approved
0.7328	Intermediate Similarity	NPD3444	Approved
0.7328	Intermediate Similarity	NPD3445	Approved
0.7328	Intermediate Similarity	NPD3443	Approved
0.7324	Intermediate Similarity	NPD1725	Approved
0.7324	Intermediate Similarity	NPD3175	Clinical (unspecified phase)
0.7319	Intermediate Similarity	NPD5718	Phase 2
0.7315	Intermediate Similarity	NPD6523	Clinical (unspecified phase)
0.731	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7305	Intermediate Similarity	NPD2200	Suspended
0.7303	Intermediate Similarity	NPD3556	Approved
0.7303	Intermediate Similarity	NPD3560	Approved
0.7303	Intermediate Similarity	NPD3558	Approved
0.7303	Intermediate Similarity	NPD3559	Clinical (unspecified phase)
0.7303	Intermediate Similarity	NPD3557	Approved
0.7299	Intermediate Similarity	NPD596	Approved
0.7299	Intermediate Similarity	NPD600	Approved
0.7288	Intermediate Similarity	NPD2934	Approved
0.7288	Intermediate Similarity	NPD2933	Approved
0.7285	Intermediate Similarity	NPD7945	Clinical (unspecified phase)
0.7279	Intermediate Similarity	NPD7905	Discontinued
0.7279	Intermediate Similarity	NPD2987	Approved
0.7279	Intermediate Similarity	NPD3985	Discontinued
0.7279	Intermediate Similarity	NPD2874	Phase 2
0.7279	Intermediate Similarity	NPD2990	Approved
0.7273	Intermediate Similarity	NPD2555	Approved
0.7273	Intermediate Similarity	NPD2550	Approved
0.7273	Intermediate Similarity	NPD2558	Approved
0.7273	Intermediate Similarity	NPD2552	Approved
0.7273	Intermediate Similarity	NPD2553	Approved
0.7273	Intermediate Similarity	NPD2549	Approved
0.7266	Intermediate Similarity	NPD6407	Approved
0.7266	Intermediate Similarity	NPD6405	Approved
0.7258	Intermediate Similarity	NPD968	Approved
0.7254	Intermediate Similarity	NPD3846	Clinical (unspecified phase)
0.7246	Intermediate Similarity	NPD3165	Approved
0.7246	Intermediate Similarity	NPD3027	Phase 3
0.7246	Intermediate Similarity	NPD3167	Approved
0.7246	Intermediate Similarity	NPD5746	Approved
0.7246	Intermediate Similarity	NPD3164	Approved
0.7246	Intermediate Similarity	NPD3166	Approved
0.7241	Intermediate Similarity	NPD7466	Approved
0.7241	Intermediate Similarity	NPD5481	Discontinued
0.7237	Intermediate Similarity	NPD7046	Clinical (unspecified phase)
0.7237	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.723	Intermediate Similarity	NPD6390	Discontinued
0.7227	Intermediate Similarity	NPD2859	Approved
0.7227	Intermediate Similarity	NPD2860	Approved
0.7226	Intermediate Similarity	NPD2861	Phase 2
0.7222	Intermediate Similarity	NPD7037	Approved
0.7219	Intermediate Similarity	NPD3796	Clinical (unspecified phase)
0.7219	Intermediate Similarity	NPD7615	Clinical (unspecified phase)
0.7214	Intermediate Similarity	NPD1558	Phase 1
0.7214	Intermediate Similarity	NPD3597	Clinical (unspecified phase)
0.7213	Intermediate Similarity	NPD4188	Approved
0.7213	Intermediate Similarity	NPD4189	Approved
0.72	Intermediate Similarity	NPD5373	Approved
0.72	Intermediate Similarity	NPD5374	Approved
0.7194	Intermediate Similarity	NPD1039	Discontinued
0.7194	Intermediate Similarity	NPD7294	Phase 1
0.7194	Intermediate Similarity	NPD6812	Clinical (unspecified phase)

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data