NPASS Compound

Structure

CID214428 OpenBabel06191716002D 24 27 0 0 1 0 0 0 0 0999 V2000 -2.3315 -0.4206 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8553 -4.8639 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4312 -0.0750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8267 -0.9080 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8267 -1.8723 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9916 -0.4259 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9916 -2.3545 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7693 -2.3498 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7322 -2.2993 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2394 -0.6101 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6448 -0.6314 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8592 -0.4378 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1565 -0.9080 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1565 -1.8723 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2441 -1.5410 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6726 -1.3902 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3247 -3.2802 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6819 -0.6819 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7083 -1.3902 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1700 -1.4401 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.2394 -2.1703 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.5897 -3.5866 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0471 -3.9189 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 3 2 0 0 0 0 2 23 1 0 0 0 0 4 5 2 0 0 0 0 4 6 1 0 0 0 0 5 7 1 0 0 0 0 6 13 2 0 0 0 0 7 14 2 0 0 0 0 8 9 1 0 0 0 0 8 15 1 0 0 0 0 9 20 1 0 0 0 0 10 13 1 0 0 0 0 10 16 2 0 0 0 0 11 18 1 0 0 0 0 11 20 1 0 0 0 0 12 19 1 0 0 0 0 12 24 1 0 0 0 0 13 14 1 0 0 0 0 14 21 1 0 0 0 0 15 18 1 1 0 0 0 15 19 1 0 0 0 0 16 19 1 0 0 0 0 16 21 1 0 0 0 0 17 22 2 0 0 0 0 17 23 1 0 0 0 0 18 3 1 6 0 0 0 18 24 1 0 0 0 0 19 17 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	326.16
Volume:	335.5
LogP:	2.019
LogD:	2.334
LogS:	-2.869
# Rotatable Bonds:	4
TPSA:	63.35
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.67
Synthetic Accessibility Score:	4.442
Fsp3:	0.421
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:	-5.58
MDCK Permeability:	1.3593619769380894e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.981
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.006
30% Bioavailability (F30%):	0.613

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.973
Plasma Protein Binding (PPB):	51.71073532104492%
Volume Distribution (VD):	2.232
Pgp-substrate:	51.65445327758789%

ADMET: Metabolism

CYP1A2-inhibitor:	0.106
CYP1A2-substrate:	0.921
CYP2C19-inhibitor:	0.162
CYP2C19-substrate:	0.81
CYP2C9-inhibitor:	0.057
CYP2C9-substrate:	0.242
CYP2D6-inhibitor:	0.824
CYP2D6-substrate:	0.48
CYP3A4-inhibitor:	0.879
CYP3A4-substrate:	0.721

ADMET: Excretion

Clearance (CL):	6.877
Half-life (T1/2):	0.307

ADMET: Toxicity

hERG Blockers:	0.656
Human Hepatotoxicity (H-HT):	0.416
Drug-inuced Liver Injury (DILI):	0.032
AMES Toxicity:	0.146
Rat Oral Acute Toxicity:	0.892
Maximum Recommended Daily Dose:	0.936
Skin Sensitization:	0.116
Carcinogencity:	0.146
Eye Corrosion:	0.003
Eye Irritation:	0.011
Respiratory Toxicity:	0.969

Download Data

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

Natural Product: NPC214428

Natural Product ID:	NPC214428
*Common Name:**	Nor-6,7-Secoangustilobine A
IUPAC Name:	methyl (3S,3aR,7aS)-7a-ethenyl-3-(1H-indol-2-yl)-2,3a,4,5,6,7-hexahydrofuro[2,3-c]pyridine-3-carboxylate
Synonyms:
Standard InCHIKey:	KZLFAYYOKRWYDO-IPELMVKDSA-N
Standard InCHI:	InChI=1S/C19H22N2O3/c1-3-18-11-20-9-8-15(18)19(12-24-18,17(22)23-2)16-10-13-6-4-5-7-14(13)21-16/h3-7,10,15,20-21H,1,8-9,11-12H2,2H3/t15-,18+,19-/m0/s1
SMILES:	C=C[C@@]12CNCC[C@@H]1[C@@](CO2)(c1cc2ccccc2[nH]1)C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1651111
PubChem CID:	53320911
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0001879] Delta amino acids and derivatives

*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
NPO17493	Alstonia spatulata	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21043460]
NPO17493	Alstonia spatulata	Species	Apocynaceae	Eukaryota	n.a.	stem	n.a.	PMID[21043460]
NPO17493	Alstonia spatulata	Species	Apocynaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21043460]
NPO17493	Alstonia spatulata	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17493	Alstonia spatulata	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17493	Alstonia spatulata	Species	Apocynaceae	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
IC50	3

Activity Type	# Activity
NON-MOLECULAR	3

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[557093]

☑ 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 NPC214428 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	294
0.1-0.2	1413
0.2-0.3	6387
0.3-0.4	21790
0.4-0.5	7551
0.5-0.6	2598
0.6-0.7	2086
0.7-0.8	540
0.8-0.85	30
0.85-0.9	5
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9617	High Similarity	NPC277350
0.9171	High Similarity	NPC55493
0.8814	High Similarity	NPC475778
0.8808	High Similarity	NPC234999
0.8777	High Similarity	NPC241024
0.8639	High Similarity	NPC474116
0.8542	High Similarity	NPC162730
0.8469	Intermediate Similarity	NPC469743
0.8466	Intermediate Similarity	NPC474121
0.8449	Intermediate Similarity	NPC329858
0.8449	Intermediate Similarity	NPC314333
0.8315	Intermediate Similarity	NPC469896
0.8238	Intermediate Similarity	NPC52557
0.8119	Intermediate Similarity	NPC472291
0.8105	Intermediate Similarity	NPC63199
0.8105	Intermediate Similarity	NPC111602
0.8105	Intermediate Similarity	NPC175474
0.8105	Intermediate Similarity	NPC102338
0.8105	Intermediate Similarity	NPC196251
0.8031	Intermediate Similarity	NPC472295
0.8031	Intermediate Similarity	NPC81802
0.8031	Intermediate Similarity	NPC472210
0.8031	Intermediate Similarity	NPC247735
0.8031	Intermediate Similarity	NPC269886
0.803	Intermediate Similarity	NPC229348
0.7989	Intermediate Similarity	NPC472119
0.7968	Intermediate Similarity	NPC219336
0.7949	Intermediate Similarity	NPC245916
0.7914	Intermediate Similarity	NPC217372
0.7914	Intermediate Similarity	NPC183662
0.7914	Intermediate Similarity	NPC15573
0.7902	Intermediate Similarity	NPC474412
0.7902	Intermediate Similarity	NPC477979
0.79	Intermediate Similarity	NPC475847
0.79	Intermediate Similarity	NPC185742
0.7897	Intermediate Similarity	NPC220151
0.7897	Intermediate Similarity	NPC19692
0.7879	Intermediate Similarity	NPC254240
0.7879	Intermediate Similarity	NPC79129
0.7879	Intermediate Similarity	NPC294909
0.7879	Intermediate Similarity	NPC81654
0.7879	Intermediate Similarity	NPC128265
0.7879	Intermediate Similarity	NPC249150
0.7879	Intermediate Similarity	NPC312870
0.7879	Intermediate Similarity	NPC195461
0.7879	Intermediate Similarity	NPC313985
0.7879	Intermediate Similarity	NPC49196
0.7879	Intermediate Similarity	NPC199851
0.7874	Intermediate Similarity	NPC96321
0.7868	Intermediate Similarity	NPC67288
0.7819	Intermediate Similarity	NPC84827
0.7819	Intermediate Similarity	NPC14113
0.7819	Intermediate Similarity	NPC145885
0.7812	Intermediate Similarity	NPC235684
0.78	Intermediate Similarity	NPC476874
0.78	Intermediate Similarity	NPC193761
0.7795	Intermediate Similarity	NPC472113
0.7788	Intermediate Similarity	NPC473041
0.7784	Intermediate Similarity	NPC472112
0.7783	Intermediate Similarity	NPC472762
0.7778	Intermediate Similarity	NPC50503
0.7778	Intermediate Similarity	NPC469928
0.7745	Intermediate Similarity	NPC478158
0.7744	Intermediate Similarity	NPC472097
0.774	Intermediate Similarity	NPC312645
0.7729	Intermediate Similarity	NPC478157
0.7723	Intermediate Similarity	NPC132539
0.7718	Intermediate Similarity	NPC118940
0.7707	Intermediate Similarity	NPC123839
0.7704	Intermediate Similarity	NPC472292
0.7692	Intermediate Similarity	NPC330009
0.7692	Intermediate Similarity	NPC36405
0.7689	Intermediate Similarity	NPC475271
0.7684	Intermediate Similarity	NPC248041
0.7684	Intermediate Similarity	NPC126709
0.7684	Intermediate Similarity	NPC213468
0.7678	Intermediate Similarity	NPC2395
0.7672	Intermediate Similarity	NPC267885
0.7653	Intermediate Similarity	NPC235885
0.7653	Intermediate Similarity	NPC138370
0.7641	Intermediate Similarity	NPC321708
0.7632	Intermediate Similarity	NPC111275
0.7629	Intermediate Similarity	NPC315555
0.7629	Intermediate Similarity	NPC160381
0.7624	Intermediate Similarity	NPC137589
0.7619	Intermediate Similarity	NPC281049
0.7619	Intermediate Similarity	NPC203468
0.7619	Intermediate Similarity	NPC110500
0.7619	Intermediate Similarity	NPC82070
0.7619	Intermediate Similarity	NPC149155
0.761	Intermediate Similarity	NPC266249
0.7608	Intermediate Similarity	NPC148183
0.7608	Intermediate Similarity	NPC152768
0.7606	Intermediate Similarity	NPC64216
0.7604	Intermediate Similarity	NPC71037
0.7596	Intermediate Similarity	NPC54744
0.7596	Intermediate Similarity	NPC89508
0.7594	Intermediate Similarity	NPC78020
0.7592	Intermediate Similarity	NPC283219
0.7588	Intermediate Similarity	NPC472293
0.7586	Intermediate Similarity	NPC476098
0.7579	Intermediate Similarity	NPC84347
0.7577	Intermediate Similarity	NPC472107
0.7577	Intermediate Similarity	NPC79062
0.7565	Intermediate Similarity	NPC143533
0.7562	Intermediate Similarity	NPC472297
0.7562	Intermediate Similarity	NPC472296
0.7561	Intermediate Similarity	NPC477065
0.7548	Intermediate Similarity	NPC472098
0.7546	Intermediate Similarity	NPC311906
0.7537	Intermediate Similarity	NPC260900
0.7523	Intermediate Similarity	NPC474192
0.7523	Intermediate Similarity	NPC475720
0.75	Intermediate Similarity	NPC165599
0.75	Intermediate Similarity	NPC55772
0.75	Intermediate Similarity	NPC52254
0.75	Intermediate Similarity	NPC472323
0.7476	Intermediate Similarity	NPC474905
0.7476	Intermediate Similarity	NPC313640
0.7475	Intermediate Similarity	NPC74413
0.7475	Intermediate Similarity	NPC293917
0.7474	Intermediate Similarity	NPC469358
0.7474	Intermediate Similarity	NPC19679
0.7474	Intermediate Similarity	NPC472108
0.7474	Intermediate Similarity	NPC139291
0.7465	Intermediate Similarity	NPC33949
0.7465	Intermediate Similarity	NPC472099
0.7462	Intermediate Similarity	NPC46413
0.7461	Intermediate Similarity	NPC91179
0.7452	Intermediate Similarity	NPC471304
0.745	Intermediate Similarity	NPC57994
0.745	Intermediate Similarity	NPC289299
0.745	Intermediate Similarity	NPC276517
0.7448	Intermediate Similarity	NPC211997
0.7446	Intermediate Similarity	NPC285469
0.7441	Intermediate Similarity	NPC476114
0.7438	Intermediate Similarity	NPC252338
0.7433	Intermediate Similarity	NPC271797
0.7433	Intermediate Similarity	NPC21174
0.7429	Intermediate Similarity	NPC234078
0.7429	Intermediate Similarity	NPC221100
0.7427	Intermediate Similarity	NPC18661
0.7421	Intermediate Similarity	NPC6982
0.7419	Intermediate Similarity	NPC475258
0.7415	Intermediate Similarity	NPC98715
0.7413	Intermediate Similarity	NPC472116
0.7413	Intermediate Similarity	NPC79356
0.7413	Intermediate Similarity	NPC102592
0.7413	Intermediate Similarity	NPC11445
0.7409	Intermediate Similarity	NPC473105
0.7409	Intermediate Similarity	NPC472443
0.7407	Intermediate Similarity	NPC317430
0.74	Intermediate Similarity	NPC88315
0.7396	Intermediate Similarity	NPC134586
0.7391	Intermediate Similarity	NPC244741
0.7385	Intermediate Similarity	NPC472444
0.7382	Intermediate Similarity	NPC34508
0.7381	Intermediate Similarity	NPC87856
0.7381	Intermediate Similarity	NPC151976
0.7381	Intermediate Similarity	NPC75634
0.7376	Intermediate Similarity	NPC141454
0.7376	Intermediate Similarity	NPC227582
0.7373	Intermediate Similarity	NPC475338
0.7373	Intermediate Similarity	NPC909
0.7371	Intermediate Similarity	NPC15840
0.7366	Intermediate Similarity	NPC155143
0.7364	Intermediate Similarity	NPC471303
0.7363	Intermediate Similarity	NPC85066
0.7363	Intermediate Similarity	NPC195239
0.7363	Intermediate Similarity	NPC157828
0.7363	Intermediate Similarity	NPC181502
0.736	Intermediate Similarity	NPC62749
0.736	Intermediate Similarity	NPC66210
0.736	Intermediate Similarity	NPC99428
0.7358	Intermediate Similarity	NPC14325
0.7358	Intermediate Similarity	NPC132211
0.7358	Intermediate Similarity	NPC203614
0.7358	Intermediate Similarity	NPC28848
0.7358	Intermediate Similarity	NPC204491
0.7358	Intermediate Similarity	NPC74969
0.7356	Intermediate Similarity	NPC127677
0.7356	Intermediate Similarity	NPC258062
0.7354	Intermediate Similarity	NPC470785
0.7354	Intermediate Similarity	NPC470509
0.735	Intermediate Similarity	NPC67551
0.7347	Intermediate Similarity	NPC472294
0.7347	Intermediate Similarity	NPC284678
0.7347	Intermediate Similarity	NPC258480
0.7346	Intermediate Similarity	NPC267965
0.7344	Intermediate Similarity	NPC472586
0.734	Intermediate Similarity	NPC306376
0.734	Intermediate Similarity	NPC149708
0.7333	Intermediate Similarity	NPC473540
0.733	Intermediate Similarity	NPC476115
0.733	Intermediate Similarity	NPC70155
0.7327	Intermediate Similarity	NPC21638
0.7324	Intermediate Similarity	NPC249428
0.7324	Intermediate Similarity	NPC305984
0.7321	Intermediate Similarity	NPC271862
0.7321	Intermediate Similarity	NPC475816

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 NPC214428 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	172
0.1-0.2	490
0.2-0.3	644
0.3-0.4	1581
0.4-0.5	2792
0.5-0.6	2646
0.6-0.7	719
0.7-0.8	102
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
0.8474	Intermediate Similarity	NPD5003	Discontinued
0.8449	Intermediate Similarity	NPD4499	Approved
0.8254	Intermediate Similarity	NPD2564	Approved
0.8254	Intermediate Similarity	NPD2565	Phase 2
0.8122	Intermediate Similarity	NPD2121	Clinical (unspecified phase)
0.805	Intermediate Similarity	NPD2509	Approved
0.805	Intermediate Similarity	NPD2510	Approved
0.794	Intermediate Similarity	NPD6176	Phase 1
0.7879	Intermediate Similarity	NPD4601	Approved
0.7879	Intermediate Similarity	NPD4500	Approved
0.7879	Intermediate Similarity	NPD4501	Approved
0.7879	Intermediate Similarity	NPD4600	Approved
0.7861	Intermediate Similarity	NPD4862	Clinical (unspecified phase)
0.785	Intermediate Similarity	NPD2920	Discontinued
0.7843	Intermediate Similarity	NPD7470	Discontinued
0.7692	Intermediate Similarity	NPD3394	Approved
0.7692	Intermediate Similarity	NPD3389	Approved
0.7692	Intermediate Similarity	NPD3393	Approved
0.7688	Intermediate Similarity	NPD2844	Phase 3
0.7672	Intermediate Similarity	NPD749	Clinical (unspecified phase)
0.7667	Intermediate Similarity	NPD6770	Approved
0.7656	Intermediate Similarity	NPD2095	Phase 2
0.7656	Intermediate Similarity	NPD5728	Clinical (unspecified phase)
0.7656	Intermediate Similarity	NPD2092	Phase 2
0.7656	Intermediate Similarity	NPD2094	Phase 2
0.7619	Intermediate Similarity	NPD482	Approved
0.7617	Intermediate Similarity	NPD2091	Phase 2
0.7617	Intermediate Similarity	NPD2096	Phase 2
0.7573	Intermediate Similarity	NPD4506	Discontinued
0.7563	Intermediate Similarity	NPD5913	Phase 3
0.7563	Intermediate Similarity	NPD5912	Clinical (unspecified phase)
0.7536	Intermediate Similarity	NPD5632	Approved
0.7512	Intermediate Similarity	NPD4987	Clinical (unspecified phase)
0.7475	Intermediate Similarity	NPD7621	Clinical (unspecified phase)
0.7475	Intermediate Similarity	NPD6630	Clinical (unspecified phase)
0.7463	Intermediate Similarity	NPD5426	Phase 3
0.745	Intermediate Similarity	NPD4602	Approved
0.7415	Intermediate Similarity	NPD8072	Approved
0.7391	Intermediate Similarity	NPD5257	Clinical (unspecified phase)
0.7389	Intermediate Similarity	NPD6661	Clinical (unspecified phase)
0.7385	Intermediate Similarity	NPD5596	Phase 2
0.7382	Intermediate Similarity	NPD750	Phase 2
0.7381	Intermediate Similarity	NPD6657	Clinical (unspecified phase)
0.7374	Intermediate Similarity	NPD4334	Discontinued
0.7366	Intermediate Similarity	NPD8073	Approved
0.7356	Intermediate Similarity	NPD8399	Phase 1
0.7356	Intermediate Similarity	NPD8423	Phase 2
0.7345	Intermediate Similarity	NPD5483	Clinical (unspecified phase)
0.7333	Intermediate Similarity	NPD5475	Discontinued
0.7321	Intermediate Similarity	NPD2921	Clinical (unspecified phase)
0.7315	Intermediate Similarity	NPD6160	Clinical (unspecified phase)
0.7311	Intermediate Similarity	NPD5293	Phase 2
0.7304	Intermediate Similarity	NPD6248	Phase 2
0.7304	Intermediate Similarity	NPD6249	Phase 2
0.7295	Intermediate Similarity	NPD8282	Approved
0.7295	Intermediate Similarity	NPD56	Approved
0.7295	Intermediate Similarity	NPD8283	Approved
0.7295	Intermediate Similarity	NPD8098	Approved
0.7268	Intermediate Similarity	NPD484	Approved
0.7265	Intermediate Similarity	NPD3006	Discontinued
0.726	Intermediate Similarity	NPD7958	Clinical (unspecified phase)
0.726	Intermediate Similarity	NPD7001	Phase 3
0.726	Intermediate Similarity	NPD7957	Phase 1
0.7255	Intermediate Similarity	NPD53	Approved
0.7255	Intermediate Similarity	NPD7778	Approved
0.7255	Intermediate Similarity	NPD7777	Approved
0.724	Intermediate Similarity	NPD7688	Phase 1
0.7231	Intermediate Similarity	NPD8467	Approved
0.7231	Intermediate Similarity	NPD8466	Approved
0.7231	Intermediate Similarity	NPD8465	Approved
0.723	Intermediate Similarity	NPD8112	Clinical (unspecified phase)
0.7217	Intermediate Similarity	NPD5482	Discontinued
0.7216	Intermediate Similarity	NPD5104	Approved
0.7212	Intermediate Similarity	NPD5901	Discontinued
0.7205	Intermediate Similarity	NPD8358	Approved
0.7204	Intermediate Similarity	NPD4900	Clinical (unspecified phase)
0.7198	Intermediate Similarity	NPD5721	Clinical (unspecified phase)
0.7197	Intermediate Similarity	NPD8364	Approved
0.7197	Intermediate Similarity	NPD8363	Approved
0.7192	Intermediate Similarity	NPD4427	Phase 2
0.7188	Intermediate Similarity	NPD4184	Clinical (unspecified phase)
0.7186	Intermediate Similarity	NPD5444	Phase 1
0.7186	Intermediate Similarity	NPD5256	Discontinued
0.7184	Intermediate Similarity	NPD6479	Discontinued
0.7178	Intermediate Similarity	NPD4315	Phase 2
0.7177	Intermediate Similarity	NPD4901	Clinical (unspecified phase)
0.7171	Intermediate Similarity	NPD7946	Pre-registration
0.717	Intermediate Similarity	NPD8013	Clinical (unspecified phase)
0.7163	Intermediate Similarity	NPD8326	Phase 3
0.7163	Intermediate Similarity	NPD8325	Phase 3
0.7163	Intermediate Similarity	NPD8327	Clinical (unspecified phase)
0.7163	Intermediate Similarity	NPD5487	Phase 1
0.7157	Intermediate Similarity	NPD5512	Phase 3
0.7156	Intermediate Similarity	NPD2125	Clinical (unspecified phase)
0.715	Intermediate Similarity	NPD6739	Clinical (unspecified phase)
0.715	Intermediate Similarity	NPD4948	Discontinued
0.7143	Intermediate Similarity	NPD1996	Discontinued
0.7137	Intermediate Similarity	NPD8365	Clinical (unspecified phase)
0.7129	Intermediate Similarity	NPD3947	Discontinued
0.7123	Intermediate Similarity	NPD7825	Clinical (unspecified phase)
0.7123	Intermediate Similarity	NPD7809	Clinical (unspecified phase)
0.712	Intermediate Similarity	NPD2915	Discontinued
0.7114	Intermediate Similarity	NPD8459	Approved
0.7114	Intermediate Similarity	NPD8425	Approved
0.7114	Intermediate Similarity	NPD1534	Approved
0.7114	Intermediate Similarity	NPD8460	Approved
0.7114	Intermediate Similarity	NPD8426	Approved
0.7107	Intermediate Similarity	NPD6595	Phase 3
0.7098	Intermediate Similarity	NPD1326	Approved
0.7098	Intermediate Similarity	NPD1325	Approved
0.7095	Intermediate Similarity	NPD3003	Approved
0.7092	Intermediate Similarity	NPD2144	Approved
0.709	Intermediate Similarity	NPD8429	Approved
0.709	Intermediate Similarity	NPD2213	Approved
0.709	Intermediate Similarity	NPD2214	Approved
0.709	Intermediate Similarity	NPD8427	Approved
0.709	Intermediate Similarity	NPD8428	Approved
0.7085	Intermediate Similarity	NPD8372	Clinical (unspecified phase)
0.7071	Intermediate Similarity	NPD3038	Discontinued
0.7067	Intermediate Similarity	NPD7903	Clinical (unspecified phase)
0.7062	Intermediate Similarity	NPD5472	Clinical (unspecified phase)
0.7056	Intermediate Similarity	NPD8096	Phase 3
0.7056	Intermediate Similarity	NPD7594	Clinical (unspecified phase)
0.7056	Intermediate Similarity	NPD8097	Phase 3
0.7054	Intermediate Similarity	NPD6263	Clinical (unspecified phase)
0.7053	Intermediate Similarity	NPD4118	Clinical (unspecified phase)
0.7053	Intermediate Similarity	NPD3800	Clinical (unspecified phase)
0.7044	Intermediate Similarity	NPD3785	Clinical (unspecified phase)
0.7044	Intermediate Similarity	NPD5592	Clinical (unspecified phase)
0.7043	Intermediate Similarity	NPD3833	Phase 3
0.7043	Intermediate Similarity	NPD3835	Phase 3
0.7042	Intermediate Similarity	NPD7998	Clinical (unspecified phase)
0.7037	Intermediate Similarity	NPD8160	Phase 2
0.7035	Intermediate Similarity	NPD5891	Approved
0.7027	Intermediate Similarity	NPD6292	Clinical (unspecified phase)
0.702	Intermediate Similarity	NPD5899	Approved
0.702	Intermediate Similarity	NPD5898	Approved
0.702	Intermediate Similarity	NPD5897	Approved
0.702	Intermediate Similarity	NPD8464	Clinical (unspecified phase)
0.7009	Intermediate Similarity	NPD5416	Discontinued
0.7005	Intermediate Similarity	NPD8406	Clinical (unspecified phase)
0.7005	Intermediate Similarity	NPD6641	Approved
0.7005	Intermediate Similarity	NPD6642	Approved
0.7004	Intermediate Similarity	NPD7955	Approved
0.7004	Intermediate Similarity	NPD7956	Approved
0.7	Intermediate Similarity	NPD6995	Phase 1
0.7	Intermediate Similarity	NPD6824	Clinical (unspecified phase)
0.6995	Remote Similarity	NPD4520	Approved
0.6991	Remote Similarity	NPD7970	Approved
0.6991	Remote Similarity	NPD5417	Clinical (unspecified phase)
0.6991	Remote Similarity	NPD7971	Clinical (unspecified phase)
0.6986	Remote Similarity	NPD6242	Discontinued
0.6978	Remote Similarity	NPD4885	Approved
0.6977	Remote Similarity	NPD7454	Approved
0.6977	Remote Similarity	NPD7455	Approved
0.6976	Remote Similarity	NPD1038	Approved
0.6976	Remote Similarity	NPD1304	Clinical (unspecified phase)
0.6975	Remote Similarity	NPD7708	Approved
0.6972	Remote Similarity	NPD7878	Phase 2
0.6971	Remote Similarity	NPD7000	Clinical (unspecified phase)
0.6971	Remote Similarity	NPD1768	Approved
0.6971	Remote Similarity	NPD6999	Discontinued
0.6965	Remote Similarity	NPD5075	Discontinued
0.6965	Remote Similarity	NPD6610	Clinical (unspecified phase)
0.6964	Remote Similarity	NPD7824	Approved
0.6957	Remote Similarity	NPD6206	Phase 1
0.6954	Remote Similarity	NPD2381	Approved
0.6954	Remote Similarity	NPD5471	Phase 3
0.6954	Remote Similarity	NPD2382	Approved
0.6954	Remote Similarity	NPD2380	Approved
0.6952	Remote Similarity	NPD4462	Approved
0.6952	Remote Similarity	NPD4463	Approved
0.6948	Remote Similarity	NPD7947	Clinical (unspecified phase)
0.6947	Remote Similarity	NPD2581	Approved
0.6947	Remote Similarity	NPD2582	Approved
0.6944	Remote Similarity	NPD3794	Approved
0.6944	Remote Similarity	NPD3795	Approved
0.6942	Remote Similarity	NPD7618	Phase 3
0.6942	Remote Similarity	NPD3324	Clinical (unspecified phase)
0.6942	Remote Similarity	NPD7619	Phase 3
0.6935	Remote Similarity	NPD5473	Discontinued
0.6934	Remote Similarity	NPD7010	Phase 3
0.6934	Remote Similarity	NPD6732	Clinical (unspecified phase)
0.693	Remote Similarity	NPD6567	Clinical (unspecified phase)
0.6929	Remote Similarity	NPD7803	Approved
0.6923	Remote Similarity	NPD1573	Approved
0.6923	Remote Similarity	NPD6261	Phase 3
0.6923	Remote Similarity	NPD1575	Approved
0.6923	Remote Similarity	NPD4397	Phase 1
0.6916	Remote Similarity	NPD7941	Phase 3
0.6916	Remote Similarity	NPD6529	Discontinued
0.6912	Remote Similarity	NPD4897	Phase 2
0.6912	Remote Similarity	NPD5903	Approved
0.6912	Remote Similarity	NPD5902	Approved
0.6908	Remote Similarity	NPD7818	Clinical (unspecified phase)
0.6907	Remote Similarity	NPD4174	Clinical (unspecified phase)
0.6907	Remote Similarity	NPD4554	Clinical (unspecified phase)
0.6905	Remote Similarity	NPD7727	Phase 2
0.6904	Remote Similarity	NPD5065	Approved
0.6901	Remote Similarity	NPD6838	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