NPASS Compound

Structure

NPC476441 OpenBabel07101718312D 27 32 0 0 1 0 0 0 0 0999 V2000 2.9523 -0.7109 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5392 -3.5024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0578 2.6451 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0876 -0.2085 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7703 -1.5971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7741 -2.3172 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1449 -1.2403 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1524 -2.6805 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9162 -1.3438 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1366 -1.6123 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2188 -1.2133 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2202 -0.7061 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5231 -1.6036 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7817 -0.4513 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5269 -2.3237 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3023 -2.0055 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6540 -0.7565 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4169 -1.9694 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9216 -0.3882 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.3066 0.9518 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8371 -1.3846 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8432 -2.5498 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7789 -1.4657 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -1.7773 0.1292 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2842 1.1622 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3644 1.6933 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 4 1 0 0 0 0 2 23 1 0 0 0 0 3 27 1 0 0 0 0 4 12 2 0 0 0 0 5 6 2 0 0 0 0 5 7 1 0 0 0 0 6 8 1 0 0 0 0 7 13 2 0 0 0 0 8 15 2 0 0 0 0 9 14 1 0 0 0 0 10 17 1 0 0 0 0 11 12 1 0 0 0 0 11 24 1 0 0 0 0 12 14 1 0 0 0 0 13 15 1 0 0 0 0 13 21 1 0 0 0 0 14 22 1 6 0 0 0 15 23 1 0 0 0 0 16 9 1 1 0 0 0 16 18 1 0 0 0 0 16 24 1 0 0 0 0 17 22 1 1 0 0 0 17 24 1 0 0 0 0 18 21 1 1 0 0 0 18 23 1 0 0 0 0 19 21 1 0 0 0 0 19 22 1 0 0 0 0 19 25 1 0 0 0 0 20 26 2 0 0 0 0 20 27 1 0 0 0 0 21 10 1 6 0 0 0 22 20 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	366.19
Volume:	372.911
LogP:	1.676
LogD:	1.653
LogS:	-3.077
# Rotatable Bonds:	2
TPSA:	53.01
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	7
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.606
Synthetic Accessibility Score:	6.619
Fsp3:	0.591
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:	-5.049
MDCK Permeability:	4.1055322071770206e-05
Pgp-inhibitor:	0.015
Pgp-substrate:	0.987
Human Intestinal Absorption (HIA):	0.946
20% Bioavailability (F20%):	0.755
30% Bioavailability (F30%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.967
Plasma Protein Binding (PPB):	63.20686340332031%
Volume Distribution (VD):	3.274
Pgp-substrate:	29.3604736328125%

ADMET: Metabolism

CYP1A2-inhibitor:	0.075
CYP1A2-substrate:	0.118
CYP2C19-inhibitor:	0.099
CYP2C19-substrate:	0.924
CYP2C9-inhibitor:	0.053
CYP2C9-substrate:	0.085
CYP2D6-inhibitor:	0.362
CYP2D6-substrate:	0.847
CYP3A4-inhibitor:	0.686
CYP3A4-substrate:	0.815

ADMET: Excretion

Clearance (CL):	8.429
Half-life (T1/2):	0.171

ADMET: Toxicity

hERG Blockers:	0.026
Human Hepatotoxicity (H-HT):	0.338
Drug-inuced Liver Injury (DILI):	0.182
AMES Toxicity:	0.053
Rat Oral Acute Toxicity:	0.938
Maximum Recommended Daily Dose:	0.943
Skin Sensitization:	0.328
Carcinogencity:	0.925
Eye Corrosion:	0.005
Eye Irritation:	0.015
Respiratory Toxicity:	0.988

Download Data

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

Natural Product: NPC476441

Natural Product ID:	NPC476441
*Common Name:**	Vincamajine
IUPAC Name:	n.a.
Synonyms:	Vincamajine
Standard InCHIKey:	DOUQNGAJTIRQPP-PRDXYIPKSA-N
Standard InCHI:	InChI=1S/C22H26N2O3/c1-4-12-11-24-16-9-14(12)22(20(26)27-3)17(24)10-21(19(22)25)13-7-5-6-8-15(13)23(2)18(16)21/h4-8,14,16-19,25H,9-11H2,1-3H3/b12-4+/t14-,16-,17-,18+,19?,21+,22-/m0/s1
SMILES:	CC=C1CN2C3CC1C4(C2CC5(C3N(C6=CC=CC=C65)C)C4O)C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL607365
PubChem CID:	46229135
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002750] Corynanthean-type alkaloids

*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
NPO19678	Alstonia macrophylla	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19191551]
NPO19678	Alstonia macrophylla	Species	Apocynaceae	Eukaryota	leaves	Purwodadi Botanical Garden, Indonesia	n.a.	PMID[20189404]
NPO19678	Alstonia macrophylla	Species	Apocynaceae	Eukaryota	n.a.	stem	n.a.	PMID[22148233]
NPO19678	Alstonia macrophylla	Species	Apocynaceae	Eukaryota	Barks	n.a.	n.a.	PMID[23806072]
NPO19678	Alstonia macrophylla	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19678	Alstonia macrophylla	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19678	Alstonia macrophylla	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO19678	Alstonia macrophylla	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	1
Others	3

Activity Type	# Activity
Individual Protein	3
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT459	Individual Protein	Human immunodeficiency virus type 1 reverse transcriptase	Human immunodeficiency virus 1	IC50	>	200.0	ug.mL-1	PMID[521023]
NPT640	Individual Protein	Sodium/glucose cotransporter 1	Homo sapiens	Inhibition	=	11.5	%	PMID[521024]
NPT641	Individual Protein	Sodium/glucose cotransporter 2	Homo sapiens	Inhibition	=	30.6	%	PMID[521024]
NPT27	Others	Unspecified		log Pe	=	-4.99	n.a.	PMID[521026]

☑ 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 NPC476441 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	234
0.1-0.2	1091
0.2-0.3	2991
0.3-0.4	17166
0.4-0.5	16421
0.5-0.6	3873
0.6-0.7	722
0.7-0.8	180
0.8-0.85	13
0.85-0.9	1
0.9-0.95	2
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9623	High Similarity	NPC476425
0.9509	High Similarity	NPC476428
0.9207	High Similarity	NPC476326
0.9045	High Similarity	NPC478076
0.8333	Intermediate Similarity	NPC472114
0.8333	Intermediate Similarity	NPC472115
0.8176	Intermediate Similarity	NPC469462
0.8166	Intermediate Similarity	NPC472106
0.8136	Intermediate Similarity	NPC472209
0.8034	Intermediate Similarity	NPC469460
0.7941	Intermediate Similarity	NPC472101
0.7941	Intermediate Similarity	NPC472120
0.7917	Intermediate Similarity	NPC29285
0.7833	Intermediate Similarity	NPC52262
0.7766	Intermediate Similarity	NPC475489
0.7765	Intermediate Similarity	NPC153694
0.7765	Intermediate Similarity	NPC113946
0.7765	Intermediate Similarity	NPC211525
0.7754	Intermediate Similarity	NPC52557
0.7746	Intermediate Similarity	NPC52059
0.7746	Intermediate Similarity	NPC470069
0.7719	Intermediate Similarity	NPC243673
0.7719	Intermediate Similarity	NPC148468
0.7719	Intermediate Similarity	NPC63210
0.7719	Intermediate Similarity	NPC263709
0.7719	Intermediate Similarity	NPC469461
0.7719	Intermediate Similarity	NPC310403
0.7719	Intermediate Similarity	NPC97380
0.7674	Intermediate Similarity	NPC225319
0.7674	Intermediate Similarity	NPC474058
0.763	Intermediate Similarity	NPC282339
0.763	Intermediate Similarity	NPC176983
0.763	Intermediate Similarity	NPC99632
0.763	Intermediate Similarity	NPC472117
0.7627	Intermediate Similarity	NPC298851
0.7627	Intermediate Similarity	NPC181138
0.7627	Intermediate Similarity	NPC210415
0.7627	Intermediate Similarity	NPC21752
0.7627	Intermediate Similarity	NPC276993
0.7627	Intermediate Similarity	NPC293255
0.7606	Intermediate Similarity	NPC90967
0.7594	Intermediate Similarity	NPC221687
0.7572	Intermediate Similarity	NPC472102
0.7572	Intermediate Similarity	NPC309531
0.7568	Intermediate Similarity	NPC105055
0.7568	Intermediate Similarity	NPC22689
0.7556	Intermediate Similarity	NPC99043
0.7556	Intermediate Similarity	NPC218594
0.7545	Intermediate Similarity	NPC472100
0.7544	Intermediate Similarity	NPC161827
0.7528	Intermediate Similarity	NPC139085
0.7528	Intermediate Similarity	NPC251212
0.7528	Intermediate Similarity	NPC214626
0.7527	Intermediate Similarity	NPC477159
0.7514	Intermediate Similarity	NPC472118
0.75	Intermediate Similarity	NPC476436
0.746	Intermediate Similarity	NPC97100
0.746	Intermediate Similarity	NPC473375
0.7429	Intermediate Similarity	NPC472121
0.7429	Intermediate Similarity	NPC286871
0.7421	Intermediate Similarity	NPC475559
0.7414	Intermediate Similarity	NPC36495
0.7391	Intermediate Similarity	NPC97584
0.7366	Intermediate Similarity	NPC21425
0.7358	Intermediate Similarity	NPC471512
0.7348	Intermediate Similarity	NPC264482
0.7348	Intermediate Similarity	NPC203202
0.7341	Intermediate Similarity	NPC473297
0.7326	Intermediate Similarity	NPC175474
0.7321	Intermediate Similarity	NPC476429
0.7314	Intermediate Similarity	NPC193410
0.7312	Intermediate Similarity	NPC282092
0.7308	Intermediate Similarity	NPC260075
0.7306	Intermediate Similarity	NPC195461
0.7306	Intermediate Similarity	NPC313985
0.7306	Intermediate Similarity	NPC81654
0.7306	Intermediate Similarity	NPC249150
0.7306	Intermediate Similarity	NPC79129
0.7306	Intermediate Similarity	NPC49196
0.7303	Intermediate Similarity	NPC279527
0.7303	Intermediate Similarity	NPC214960
0.7293	Intermediate Similarity	NPC13367
0.7283	Intermediate Similarity	NPC475962
0.7273	Intermediate Similarity	NPC472323
0.7273	Intermediate Similarity	NPC143457
0.7273	Intermediate Similarity	NPC248117
0.7273	Intermediate Similarity	NPC181928
0.7263	Intermediate Similarity	NPC224970
0.7263	Intermediate Similarity	NPC167724
0.7263	Intermediate Similarity	NPC223595
0.7258	Intermediate Similarity	NPC472107
0.7258	Intermediate Similarity	NPC79062
0.7257	Intermediate Similarity	NPC61013
0.7247	Intermediate Similarity	NPC471124
0.724	Intermediate Similarity	NPC302548
0.7238	Intermediate Similarity	NPC96901
0.7232	Intermediate Similarity	NPC85651
0.7228	Intermediate Similarity	NPC15840
0.7225	Intermediate Similarity	NPC34717
0.7225	Intermediate Similarity	NPC289299
0.7225	Intermediate Similarity	NPC57994
0.7216	Intermediate Similarity	NPC471122
0.7207	Intermediate Similarity	NPC278887
0.7204	Intermediate Similarity	NPC472119
0.7204	Intermediate Similarity	NPC245741
0.7202	Intermediate Similarity	NPC50503
0.7196	Intermediate Similarity	NPC473298
0.7194	Intermediate Similarity	NPC477179
0.7193	Intermediate Similarity	NPC212799
0.7191	Intermediate Similarity	NPC313757
0.7174	Intermediate Similarity	NPC6974
0.7157	Intermediate Similarity	NPC254850
0.7157	Intermediate Similarity	NPC477178
0.7157	Intermediate Similarity	NPC477180
0.7157	Intermediate Similarity	NPC477181
0.7151	Intermediate Similarity	NPC159963
0.715	Intermediate Similarity	NPC162440
0.7143	Intermediate Similarity	NPC284706
0.7136	Intermediate Similarity	NPC471945
0.7136	Intermediate Similarity	NPC471950
0.7135	Intermediate Similarity	NPC293458
0.7121	Intermediate Similarity	NPC470490
0.7121	Intermediate Similarity	NPC477173
0.7121	Intermediate Similarity	NPC477174
0.712	Intermediate Similarity	NPC186669
0.7118	Intermediate Similarity	NPC472103
0.71	Intermediate Similarity	NPC471946
0.71	Intermediate Similarity	NPC471951
0.709	Intermediate Similarity	NPC14994
0.7085	Intermediate Similarity	NPC470488
0.7079	Intermediate Similarity	NPC315368
0.7071	Intermediate Similarity	NPC329833
0.7068	Intermediate Similarity	NPC25401
0.7065	Intermediate Similarity	NPC191817
0.7065	Intermediate Similarity	NPC475359
0.7062	Intermediate Similarity	NPC123241
0.7059	Intermediate Similarity	NPC143533
0.705	Intermediate Similarity	NPC475259
0.7049	Intermediate Similarity	NPC285622
0.7044	Intermediate Similarity	NPC291027
0.7044	Intermediate Similarity	NPC84281
0.7044	Intermediate Similarity	NPC317474
0.7044	Intermediate Similarity	NPC169485
0.7044	Intermediate Similarity	NPC213126
0.7041	Intermediate Similarity	NPC138830
0.7041	Intermediate Similarity	NPC470301
0.7035	Intermediate Similarity	NPC264589
0.7033	Intermediate Similarity	NPC469915
0.7	Intermediate Similarity	NPC471516
0.6989	Remote Similarity	NPC133261
0.6983	Remote Similarity	NPC201424
0.6979	Remote Similarity	NPC472097
0.6976	Remote Similarity	NPC234772
0.6973	Remote Similarity	NPC472122
0.6973	Remote Similarity	NPC24594
0.6968	Remote Similarity	NPC472104
0.6957	Remote Similarity	NPC288110
0.6954	Remote Similarity	NPC67904
0.6952	Remote Similarity	NPC472105
0.6952	Remote Similarity	NPC187827
0.6947	Remote Similarity	NPC478077
0.6931	Remote Similarity	NPC258480
0.6927	Remote Similarity	NPC5630
0.6927	Remote Similarity	NPC473569
0.6927	Remote Similarity	NPC474059
0.6919	Remote Similarity	NPC469726
0.6919	Remote Similarity	NPC311330
0.6919	Remote Similarity	NPC329338
0.6905	Remote Similarity	NPC471123
0.6891	Remote Similarity	NPC203628
0.6884	Remote Similarity	NPC162730
0.6884	Remote Similarity	NPC471436
0.6884	Remote Similarity	NPC1464
0.6882	Remote Similarity	NPC129624
0.6881	Remote Similarity	NPC470491
0.6875	Remote Similarity	NPC154602
0.6875	Remote Similarity	NPC475763
0.6865	Remote Similarity	NPC473880
0.6863	Remote Similarity	NPC82541
0.6862	Remote Similarity	NPC11149
0.6859	Remote Similarity	NPC66210
0.6856	Remote Similarity	NPC473004
0.6837	Remote Similarity	NPC473486
0.6837	Remote Similarity	NPC475316
0.6837	Remote Similarity	NPC472116
0.6837	Remote Similarity	NPC245916
0.6829	Remote Similarity	NPC127996
0.6816	Remote Similarity	NPC470489
0.6814	Remote Similarity	NPC234999
0.6811	Remote Similarity	NPC318183
0.68	Remote Similarity	NPC474116
0.6791	Remote Similarity	NPC35390
0.6791	Remote Similarity	NPC470631
0.6791	Remote Similarity	NPC473781
0.6789	Remote Similarity	NPC472110
0.6789	Remote Similarity	NPC472108
0.6789	Remote Similarity	NPC472109
0.6789	Remote Similarity	NPC139291
0.6784	Remote Similarity	NPC243162
0.6784	Remote Similarity	NPC315051

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 NPC476441 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	152
0.1-0.2	495
0.2-0.3	721
0.3-0.4	1680
0.4-0.5	3915
0.5-0.6	1982
0.6-0.7	197
0.7-0.8	3
0.8-0.85	0
0.85-0.9	5
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8805	High Similarity	NPD4121	Phase 3
0.8805	High Similarity	NPD4120	Approved
0.875	High Similarity	NPD5743	Approved
0.875	High Similarity	NPD5741	Approved
0.875	High Similarity	NPD5742	Approved
0.7306	Intermediate Similarity	NPD4601	Approved
0.7306	Intermediate Similarity	NPD4600	Approved
0.7225	Intermediate Similarity	NPD4602	Approved
0.7044	Intermediate Similarity	NPD2609	Approved
0.7044	Intermediate Similarity	NPD2612	Approved
0.7044	Intermediate Similarity	NPD3132	Approved
0.7044	Intermediate Similarity	NPD2610	Approved
0.7044	Intermediate Similarity	NPD2608	Approved
0.7044	Intermediate Similarity	NPD4217	Approved
0.7044	Intermediate Similarity	NPD2611	Approved
0.7044	Intermediate Similarity	NPD3131	Approved
0.7044	Intermediate Similarity	NPD4216	Approved
0.7044	Intermediate Similarity	NPD4215	Approved
0.7044	Intermediate Similarity	NPD4218	Approved
0.7011	Intermediate Similarity	NPD3423	Phase 2
0.7011	Intermediate Similarity	NPD3422	Phase 3
0.6966	Remote Similarity	NPD5715	Clinical (unspecified phase)
0.6954	Remote Similarity	NPD4682	Phase 2
0.6927	Remote Similarity	NPD7599	Phase 2
0.6889	Remote Similarity	NPD7600	Phase 2
0.6886	Remote Similarity	NPD5182	Approved
0.6886	Remote Similarity	NPD5184	Approved
0.6886	Remote Similarity	NPD5185	Approved
0.6879	Remote Similarity	NPD7295	Approved
0.6821	Remote Similarity	NPD7487	Discontinued
0.6796	Remote Similarity	NPD2506	Approved
0.6784	Remote Similarity	NPD6805	Discontinued
0.678	Remote Similarity	NPD7606	Phase 3
0.6774	Remote Similarity	NPD3377	Discontinued
0.6765	Remote Similarity	NPD4520	Approved
0.6757	Remote Similarity	NPD3376	Clinical (unspecified phase)
0.6747	Remote Similarity	NPD2613	Approved
0.6744	Remote Similarity	NPD3625	Discontinued
0.6736	Remote Similarity	NPD8103	Clinical (unspecified phase)
0.6716	Remote Similarity	NPD5721	Clinical (unspecified phase)
0.67	Remote Similarity	NPD4500	Approved
0.67	Remote Similarity	NPD4501	Approved
0.6687	Remote Similarity	NPD2994	Approved
0.6684	Remote Similarity	NPD4329	Approved
0.6684	Remote Similarity	NPD4330	Approved
0.6667	Remote Similarity	NPD7082	Approved
0.6667	Remote Similarity	NPD2820	Phase 3
0.6667	Remote Similarity	NPD4499	Approved
0.6648	Remote Similarity	NPD2427	Approved
0.6648	Remote Similarity	NPD6416	Phase 2
0.6629	Remote Similarity	NPD7259	Approved
0.6627	Remote Similarity	NPD3088	Approved
0.6627	Remote Similarity	NPD2572	Clinical (unspecified phase)
0.6627	Remote Similarity	NPD3089	Approved
0.6627	Remote Similarity	NPD2573	Approved
0.6627	Remote Similarity	NPD2571	Approved
0.6627	Remote Similarity	NPD2574	Discontinued
0.6627	Remote Similarity	NPD3615	Approved
0.6627	Remote Similarity	NPD4745	Approved
0.6627	Remote Similarity	NPD4746	Phase 3
0.6627	Remote Similarity	NPD3087	Approved
0.6627	Remote Similarity	NPD3090	Approved
0.6627	Remote Similarity	NPD3616	Approved
0.6627	Remote Similarity	NPD3614	Approved
0.6627	Remote Similarity	NPD2566	Approved
0.6627	Remote Similarity	NPD2570	Approved
0.6626	Remote Similarity	NPD4775	Clinical (unspecified phase)
0.6625	Remote Similarity	NPD2115	Approved
0.6625	Remote Similarity	NPD2117	Pre-registration
0.6625	Remote Similarity	NPD2116	Approved
0.6615	Remote Similarity	NPD7962	Phase 2
0.6615	Remote Similarity	NPD8658	Clinical (unspecified phase)
0.6613	Remote Similarity	NPD2037	Approved
0.661	Remote Similarity	NPD7478	Approved
0.6609	Remote Similarity	NPD2365	Approved
0.6601	Remote Similarity	NPD7205	Discontinued
0.6591	Remote Similarity	NPD5932	Phase 3
0.6591	Remote Similarity	NPD5931	Phase 3
0.6591	Remote Similarity	NPD5933	Phase 3
0.6579	Remote Similarity	NPD3792	Approved
0.6573	Remote Similarity	NPD5942	Approved
0.6573	Remote Similarity	NPD5941	Approved
0.657	Remote Similarity	NPD2567	Approved
0.657	Remote Similarity	NPD2569	Approved
0.6567	Remote Similarity	NPD6661	Clinical (unspecified phase)
0.6564	Remote Similarity	NPD2946	Phase 2
0.6562	Remote Similarity	NPD3470	Approved
0.6562	Remote Similarity	NPD3471	Approved
0.655	Remote Similarity	NPD4684	Phase 3
0.655	Remote Similarity	NPD4685	Phase 3
0.655	Remote Similarity	NPD4686	Approved
0.6548	Remote Similarity	NPD5504	Discontinued
0.6543	Remote Similarity	NPD2432	Approved
0.6543	Remote Similarity	NPD2431	Approved
0.6543	Remote Similarity	NPD5727	Clinical (unspecified phase)
0.6543	Remote Similarity	NPD3032	Approved
0.6543	Remote Similarity	NPD3030	Approved
0.6543	Remote Similarity	NPD3031	Approved
0.6524	Remote Similarity	NPD2454	Approved
0.6524	Remote Similarity	NPD2455	Approved
0.6517	Remote Similarity	NPD7778	Approved
0.6517	Remote Similarity	NPD53	Approved
0.6517	Remote Similarity	NPD7777	Approved
0.6512	Remote Similarity	NPD6102	Clinical (unspecified phase)
0.651	Remote Similarity	NPD6878	Phase 2
0.651	Remote Similarity	NPD6879	Phase 2
0.6508	Remote Similarity	NPD5997	Discontinued
0.648	Remote Similarity	NPD5881	Clinical (unspecified phase)
0.6477	Remote Similarity	NPD5024	Approved
0.6474	Remote Similarity	NPD2670	Approved
0.6468	Remote Similarity	NPD3828	Approved
0.6458	Remote Similarity	NPD3782	Discontinued
0.644	Remote Similarity	NPD2083	Clinical (unspecified phase)
0.644	Remote Similarity	NPD8022	Clinical (unspecified phase)
0.6437	Remote Similarity	NPD3648	Clinical (unspecified phase)
0.6436	Remote Similarity	NPD2404	Discontinued
0.6436	Remote Similarity	NPD4397	Phase 1
0.6417	Remote Similarity	NPD5430	Discontinued
0.6402	Remote Similarity	NPD7168	Phase 3
0.6386	Remote Similarity	NPD1360	Approved
0.6381	Remote Similarity	NPD7595	Discontinued
0.6377	Remote Similarity	NPD4901	Clinical (unspecified phase)
0.6373	Remote Similarity	NPD2869	Clinical (unspecified phase)
0.6359	Remote Similarity	NPD1663	Discontinued
0.6359	Remote Similarity	NPD7105	Phase 1
0.6355	Remote Similarity	NPD4987	Clinical (unspecified phase)
0.6354	Remote Similarity	NPD3978	Clinical (unspecified phase)
0.6349	Remote Similarity	NPD2844	Phase 3
0.6348	Remote Similarity	NPD7488	Clinical (unspecified phase)
0.6328	Remote Similarity	NPD6566	Discontinued
0.6322	Remote Similarity	NPD5725	Approved
0.6313	Remote Similarity	NPD7683	Discontinued
0.6313	Remote Similarity	NPD6017	Discontinued
0.6312	Remote Similarity	NPD2607	Approved
0.631	Remote Similarity	NPD6792	Phase 3
0.6307	Remote Similarity	NPD989	Approved
0.6305	Remote Similarity	NPD5003	Discontinued
0.6302	Remote Similarity	NPD6316	Clinical (unspecified phase)
0.6302	Remote Similarity	NPD7449	Clinical (unspecified phase)
0.6302	Remote Similarity	NPD5466	Approved
0.6296	Remote Similarity	NPD5823	Approved
0.6292	Remote Similarity	NPD6301	Phase 2
0.6287	Remote Similarity	NPD3623	Clinical (unspecified phase)
0.6287	Remote Similarity	NPD3622	Clinical (unspecified phase)
0.6281	Remote Similarity	NPD4334	Discontinued
0.6277	Remote Similarity	NPD3790	Phase 2
0.6272	Remote Similarity	NPD2626	Approved
0.6272	Remote Similarity	NPD2160	Approved
0.6272	Remote Similarity	NPD2625	Approved
0.6272	Remote Similarity	NPD2628	Approved
0.6272	Remote Similarity	NPD2159	Approved
0.6272	Remote Similarity	NPD2627	Approved
0.6263	Remote Similarity	NPD3468	Approved
0.6257	Remote Similarity	NPD4676	Approved
0.6257	Remote Similarity	NPD5992	Approved
0.6257	Remote Similarity	NPD4365	Phase 2
0.6257	Remote Similarity	NPD2387	Approved
0.6257	Remote Similarity	NPD5918	Discontinued
0.6256	Remote Similarity	NPD5548	Clinical (unspecified phase)
0.6256	Remote Similarity	NPD5897	Approved
0.6256	Remote Similarity	NPD5899	Approved
0.6256	Remote Similarity	NPD5898	Approved
0.625	Remote Similarity	NPD3170	Approved
0.6243	Remote Similarity	NPD7714	Approved
0.6243	Remote Similarity	NPD7715	Approved
0.6243	Remote Similarity	NPD7794	Clinical (unspecified phase)
0.6243	Remote Similarity	NPD1527	Phase 2
0.6243	Remote Similarity	NPD1801	Approved
0.6243	Remote Similarity	NPD7591	Clinical (unspecified phase)
0.6243	Remote Similarity	NPD1802	Approved
0.6238	Remote Similarity	NPD2906	Approved
0.6238	Remote Similarity	NPD7666	Phase 3
0.6238	Remote Similarity	NPD4082	Approved
0.6238	Remote Similarity	NPD2907	Approved
0.6238	Remote Similarity	NPD7665	Phase 2
0.6237	Remote Similarity	NPD7735	Clinical (unspecified phase)
0.6237	Remote Similarity	NPD8630	Approved
0.6235	Remote Similarity	NPD5629	Discontinued
0.6235	Remote Similarity	NPD5993	Phase 1
0.6231	Remote Similarity	NPD8021	Approved
0.6231	Remote Similarity	NPD6891	Phase 2
0.6231	Remote Similarity	NPD8020	Approved
0.623	Remote Similarity	NPD7795	Phase 2
0.6229	Remote Similarity	NPD8173	Phase 2
0.6229	Remote Similarity	NPD8172	Phase 2
0.6229	Remote Similarity	NPD6073	Approved
0.6224	Remote Similarity	NPD7149	Clinical (unspecified phase)
0.6221	Remote Similarity	NPD1070	Approved
0.6221	Remote Similarity	NPD1069	Approved
0.622	Remote Similarity	NPD7174	Clinical (unspecified phase)
0.6219	Remote Similarity	NPD3884	Discontinued
0.6219	Remote Similarity	NPD4370	Phase 3
0.6213	Remote Similarity	NPD6320	Approved
0.6209	Remote Similarity	NPD4432	Discontinued
0.6207	Remote Similarity	NPD7944	Discontinued
0.6207	Remote Similarity	NPD6309	Approved
0.6207	Remote Similarity	NPD6310	Approved
0.6207	Remote Similarity	NPD6311	Approved
0.6203	Remote Similarity	NPD5294	Clinical (unspecified phase)
0.6201	Remote Similarity	NPD4430	Phase 2

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