NPASS Compound

Structure

NPC476428 OpenBabel07101718232D 28 33 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 0 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 1.1366 -2.3995 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 28 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 28 1 0 0 0 0 21 10 1 6 0 0 0 22 20 1 1 0 0 0 24 27 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	382.19
Volume:	381.702
LogP:	0.691
LogD:	0.742
LogS:	-1.881
# Rotatable Bonds:	2
TPSA:	72.83
# H-Bond Aceptor:	6
# H-Bond Donor:	1
# Rings:	7
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.347
Synthetic Accessibility Score:	6.937
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:	-5.569
MDCK Permeability:	8.464742131764069e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.999
Human Intestinal Absorption (HIA):	0.999
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.524
Plasma Protein Binding (PPB):	51.18769836425781%
Volume Distribution (VD):	1.167
Pgp-substrate:	39.080265045166016%

ADMET: Metabolism

CYP1A2-inhibitor:	0.027
CYP1A2-substrate:	0.11
CYP2C19-inhibitor:	0.039
CYP2C19-substrate:	0.692
CYP2C9-inhibitor:	0.017
CYP2C9-substrate:	0.084
CYP2D6-inhibitor:	0.01
CYP2D6-substrate:	0.371
CYP3A4-inhibitor:	0.073
CYP3A4-substrate:	0.426

ADMET: Excretion

Clearance (CL):	6.68
Half-life (T1/2):	0.706

ADMET: Toxicity

hERG Blockers:	0.003
Human Hepatotoxicity (H-HT):	0.16
Drug-inuced Liver Injury (DILI):	0.13
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.966
Maximum Recommended Daily Dose:	0.964
Skin Sensitization:	0.309
Carcinogencity:	0.934
Eye Corrosion:	0.015
Eye Irritation:	0.04
Respiratory Toxicity:	0.986

Download Data

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

Natural Product: NPC476428

Natural Product ID:	NPC476428
*Common Name:**	Alstiphyllanine H
IUPAC Name:	n.a.
Synonyms:	Alstiphyllanine H
Standard InCHIKey:	XTFVLFGRXGBQCC-QFGVLRAYSA-N
Standard InCHI:	InChI=1S/C22H26N2O4/c1-4-12-11-24(27)16-9-14(12)22(20(26)28-3)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-,24?/m0/s1
SMILES:	CC=C1C[N+]2(C3CC1C4(C2CC5(C3N(C6=CC=CC=C65)C)C4O)C(=O)OC)[O-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL602147
PubChem CID:	46229074
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
Others	2

Activity Type	# Activity
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT640	Individual Protein	Sodium/glucose cotransporter 1	Homo sapiens	Inhibition	=	4.3	%	PMID[450234]
NPT641	Individual Protein	Sodium/glucose cotransporter 2	Homo sapiens	Inhibition	=	23.1	%	PMID[450234]

☑ 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 NPC476428 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	1136
0.2-0.3	3054
0.3-0.4	17767
0.4-0.5	15996
0.5-0.6	3659
0.6-0.7	688
0.7-0.8	148
0.8-0.85	8
0.85-0.9	3
0.9-0.95	0
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.9691	High Similarity	NPC476326
0.9509	High Similarity	NPC476441
0.9268	High Similarity	NPC476425
0.8589	High Similarity	NPC478076
0.8571	High Similarity	NPC472209
0.8466	Intermediate Similarity	NPC469460
0.8059	Intermediate Similarity	NPC469461
0.7931	Intermediate Similarity	NPC472115
0.7931	Intermediate Similarity	NPC472114
0.7886	Intermediate Similarity	NPC469462
0.7771	Intermediate Similarity	NPC472106
0.7733	Intermediate Similarity	NPC29285
0.7557	Intermediate Similarity	NPC472120
0.7557	Intermediate Similarity	NPC472101
0.7527	Intermediate Similarity	NPC260075
0.7513	Intermediate Similarity	NPC475489
0.7486	Intermediate Similarity	NPC153694
0.7486	Intermediate Similarity	NPC211525
0.7473	Intermediate Similarity	NPC52262
0.7472	Intermediate Similarity	NPC470069
0.7472	Intermediate Similarity	NPC52059
0.7459	Intermediate Similarity	NPC477159
0.7458	Intermediate Similarity	NPC176983
0.7443	Intermediate Similarity	NPC310403
0.7443	Intermediate Similarity	NPC263709
0.7443	Intermediate Similarity	NPC148468
0.7443	Intermediate Similarity	NPC97380
0.7443	Intermediate Similarity	NPC243673
0.7443	Intermediate Similarity	NPC63210
0.7409	Intermediate Similarity	NPC52557
0.7401	Intermediate Similarity	NPC225319
0.7386	Intermediate Similarity	NPC113946
0.7363	Intermediate Similarity	NPC181138
0.7363	Intermediate Similarity	NPC276993
0.7363	Intermediate Similarity	NPC298851
0.7363	Intermediate Similarity	NPC293255
0.7363	Intermediate Similarity	NPC21752
0.7363	Intermediate Similarity	NPC210415
0.7358	Intermediate Similarity	NPC475559
0.7358	Intermediate Similarity	NPC90967
0.7344	Intermediate Similarity	NPC221687
0.7322	Intermediate Similarity	NPC329338
0.7322	Intermediate Similarity	NPC469726
0.7303	Intermediate Similarity	NPC474058
0.7297	Intermediate Similarity	NPC99043
0.7297	Intermediate Similarity	NPC218594
0.7273	Intermediate Similarity	NPC476436
0.7273	Intermediate Similarity	NPC161827
0.7263	Intermediate Similarity	NPC282339
0.7263	Intermediate Similarity	NPC472117
0.7263	Intermediate Similarity	NPC99632
0.7263	Intermediate Similarity	NPC286871
0.7249	Intermediate Similarity	NPC282092
0.7234	Intermediate Similarity	NPC97584
0.7228	Intermediate Similarity	NPC13367
0.7225	Intermediate Similarity	NPC105055
0.7225	Intermediate Similarity	NPC22689
0.7216	Intermediate Similarity	NPC97100
0.7216	Intermediate Similarity	NPC473375
0.7207	Intermediate Similarity	NPC309531
0.7207	Intermediate Similarity	NPC472102
0.7179	Intermediate Similarity	NPC302548
0.7174	Intermediate Similarity	NPC214626
0.7174	Intermediate Similarity	NPC251212
0.7174	Intermediate Similarity	NPC139085
0.7168	Intermediate Similarity	NPC472100
0.7158	Intermediate Similarity	NPC472118
0.7151	Intermediate Similarity	NPC36495
0.7143	Intermediate Similarity	NPC245741
0.7121	Intermediate Similarity	NPC471512
0.7111	Intermediate Similarity	NPC143457
0.7103	Intermediate Similarity	NPC476429
0.7102	Intermediate Similarity	NPC475763
0.7097	Intermediate Similarity	NPC203202
0.7097	Intermediate Similarity	NPC264482
0.7083	Intermediate Similarity	NPC284706
0.7079	Intermediate Similarity	NPC473297
0.7072	Intermediate Similarity	NPC472121
0.7056	Intermediate Similarity	NPC193410
0.7037	Intermediate Similarity	NPC475962
0.7031	Intermediate Similarity	NPC21425
0.7031	Intermediate Similarity	NPC472323
0.7021	Intermediate Similarity	NPC6974
0.7017	Intermediate Similarity	NPC248117
0.7011	Intermediate Similarity	NPC223595
0.7011	Intermediate Similarity	NPC167724
0.7011	Intermediate Similarity	NPC224970
0.7005	Intermediate Similarity	NPC469736
0.7	Intermediate Similarity	NPC61013
0.6995	Remote Similarity	NPC175474
0.699	Remote Similarity	NPC34717
0.6985	Remote Similarity	NPC49196
0.6985	Remote Similarity	NPC79129
0.6985	Remote Similarity	NPC249150
0.6985	Remote Similarity	NPC313985
0.6985	Remote Similarity	NPC81654
0.6985	Remote Similarity	NPC195461
0.6968	Remote Similarity	NPC186669
0.6965	Remote Similarity	NPC477179
0.6959	Remote Similarity	NPC473298
0.6957	Remote Similarity	NPC214960
0.6957	Remote Similarity	NPC279527
0.6943	Remote Similarity	NPC14994
0.6943	Remote Similarity	NPC181928
0.694	Remote Similarity	NPC313757
0.6931	Remote Similarity	NPC477178
0.6931	Remote Similarity	NPC477181
0.6931	Remote Similarity	NPC254850
0.6931	Remote Similarity	NPC477180
0.6927	Remote Similarity	NPC472107
0.6927	Remote Similarity	NPC79062
0.6912	Remote Similarity	NPC471950
0.6912	Remote Similarity	NPC471945
0.6911	Remote Similarity	NPC159963
0.6904	Remote Similarity	NPC57994
0.6904	Remote Similarity	NPC289299
0.6902	Remote Similarity	NPC471124
0.6898	Remote Similarity	NPC96901
0.6897	Remote Similarity	NPC470490
0.6897	Remote Similarity	NPC477173
0.6897	Remote Similarity	NPC477174
0.6895	Remote Similarity	NPC15840
0.6885	Remote Similarity	NPC293458
0.6885	Remote Similarity	NPC85651
0.6884	Remote Similarity	NPC50503
0.6878	Remote Similarity	NPC471946
0.6878	Remote Similarity	NPC471951
0.6875	Remote Similarity	NPC472119
0.6868	Remote Similarity	NPC471122
0.6866	Remote Similarity	NPC469732
0.6865	Remote Similarity	NPC278887
0.6863	Remote Similarity	NPC470488
0.6854	Remote Similarity	NPC318086
0.6851	Remote Similarity	NPC469536
0.6847	Remote Similarity	NPC329833
0.6847	Remote Similarity	NPC470489
0.6847	Remote Similarity	NPC185742
0.6847	Remote Similarity	NPC475847
0.6845	Remote Similarity	NPC475359
0.6845	Remote Similarity	NPC191817
0.6837	Remote Similarity	NPC25401
0.6836	Remote Similarity	NPC212799
0.6834	Remote Similarity	NPC162440
0.6831	Remote Similarity	NPC477158
0.6831	Remote Similarity	NPC315368
0.6829	Remote Similarity	NPC475259
0.6813	Remote Similarity	NPC123241
0.6802	Remote Similarity	NPC473004
0.6762	Remote Similarity	NPC234772
0.6761	Remote Similarity	NPC472103
0.6749	Remote Similarity	NPC1464
0.6745	Remote Similarity	NPC288110
0.6739	Remote Similarity	NPC201424
0.6736	Remote Similarity	NPC143533
0.6734	Remote Similarity	NPC474121
0.6733	Remote Similarity	NPC138830
0.672	Remote Similarity	NPC285622
0.6702	Remote Similarity	NPC469915
0.6701	Remote Similarity	NPC5630
0.6701	Remote Similarity	NPC474059
0.6686	Remote Similarity	NPC470301
0.6685	Remote Similarity	NPC264589
0.6667	Remote Similarity	NPC291027
0.6667	Remote Similarity	NPC133261
0.6667	Remote Similarity	NPC470491
0.6667	Remote Similarity	NPC472097
0.6667	Remote Similarity	NPC84281
0.6667	Remote Similarity	NPC317474
0.6667	Remote Similarity	NPC169485
0.6667	Remote Similarity	NPC471436
0.6667	Remote Similarity	NPC213126
0.6667	Remote Similarity	NPC203628
0.665	Remote Similarity	NPC195787
0.665	Remote Similarity	NPC230313
0.665	Remote Similarity	NPC246140
0.665	Remote Similarity	NPC67904
0.6649	Remote Similarity	NPC24594
0.6649	Remote Similarity	NPC129624
0.6649	Remote Similarity	NPC472122
0.6649	Remote Similarity	NPC472104
0.6648	Remote Similarity	NPC471516
0.6636	Remote Similarity	NPC475316
0.6636	Remote Similarity	NPC473486
0.6634	Remote Similarity	NPC138615
0.6634	Remote Similarity	NPC265642
0.6634	Remote Similarity	NPC218733
0.6634	Remote Similarity	NPC132874
0.6633	Remote Similarity	NPC478077
0.6632	Remote Similarity	NPC11149
0.6632	Remote Similarity	NPC472105
0.6632	Remote Similarity	NPC187827
0.663	Remote Similarity	NPC154602
0.6619	Remote Similarity	NPC127996
0.6618	Remote Similarity	NPC232600
0.6616	Remote Similarity	NPC473569
0.6615	Remote Similarity	NPC258480
0.6603	Remote Similarity	NPC234999
0.6602	Remote Similarity	NPC87714
0.6591	Remote Similarity	NPC473781
0.6591	Remote Similarity	NPC35390

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 NPC476428 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	151
0.1-0.2	487
0.2-0.3	737
0.3-0.4	1804
0.4-0.5	3970
0.5-0.6	1819
0.6-0.7	176
0.7-0.8	1
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
0.8364	Intermediate Similarity	NPD4121	Phase 3
0.8364	Intermediate Similarity	NPD4120	Approved
0.8313	Intermediate Similarity	NPD5742	Approved
0.8313	Intermediate Similarity	NPD5741	Approved
0.8313	Intermediate Similarity	NPD5743	Approved
0.6985	Remote Similarity	NPD4600	Approved
0.6985	Remote Similarity	NPD4601	Approved
0.6904	Remote Similarity	NPD4602	Approved
0.6893	Remote Similarity	NPD4682	Phase 2
0.6772	Remote Similarity	NPD3422	Phase 3
0.6772	Remote Similarity	NPD3423	Phase 2
0.6721	Remote Similarity	NPD5715	Clinical (unspecified phase)
0.6685	Remote Similarity	NPD7599	Phase 2
0.6667	Remote Similarity	NPD2609	Approved
0.6667	Remote Similarity	NPD2611	Approved
0.6667	Remote Similarity	NPD2608	Approved
0.6667	Remote Similarity	NPD2612	Approved
0.6667	Remote Similarity	NPD3132	Approved
0.6667	Remote Similarity	NPD2610	Approved
0.6667	Remote Similarity	NPD4217	Approved
0.6667	Remote Similarity	NPD4216	Approved
0.6667	Remote Similarity	NPD3131	Approved
0.6667	Remote Similarity	NPD4218	Approved
0.6667	Remote Similarity	NPD4215	Approved
0.6649	Remote Similarity	NPD7600	Phase 2
0.663	Remote Similarity	NPD7606	Phase 3
0.6629	Remote Similarity	NPD7295	Approved
0.6573	Remote Similarity	NPD7487	Discontinued
0.6569	Remote Similarity	NPD6805	Discontinued
0.6545	Remote Similarity	NPD3377	Discontinued
0.6532	Remote Similarity	NPD5182	Approved
0.6532	Remote Similarity	NPD5185	Approved
0.6532	Remote Similarity	NPD5184	Approved
0.6515	Remote Similarity	NPD8103	Clinical (unspecified phase)
0.6491	Remote Similarity	NPD2613	Approved
0.648	Remote Similarity	NPD7962	Phase 2
0.648	Remote Similarity	NPD8658	Clinical (unspecified phase)
0.6476	Remote Similarity	NPD4520	Approved
0.6471	Remote Similarity	NPD2506	Approved
0.6464	Remote Similarity	NPD7478	Approved
0.644	Remote Similarity	NPD3376	Clinical (unspecified phase)
0.6425	Remote Similarity	NPD5721	Clinical (unspecified phase)
0.6425	Remote Similarity	NPD7082	Approved
0.6408	Remote Similarity	NPD4500	Approved
0.6408	Remote Similarity	NPD4501	Approved
0.6404	Remote Similarity	NPD3625	Discontinued
0.6394	Remote Similarity	NPD7205	Discontinued
0.6389	Remote Similarity	NPD7259	Approved
0.6379	Remote Similarity	NPD2566	Approved
0.6379	Remote Similarity	NPD3087	Approved
0.6379	Remote Similarity	NPD3090	Approved
0.6379	Remote Similarity	NPD3614	Approved
0.6379	Remote Similarity	NPD3615	Approved
0.6379	Remote Similarity	NPD3616	Approved
0.6379	Remote Similarity	NPD3088	Approved
0.6379	Remote Similarity	NPD2572	Clinical (unspecified phase)
0.6379	Remote Similarity	NPD2573	Approved
0.6379	Remote Similarity	NPD3089	Approved
0.6379	Remote Similarity	NPD4746	Phase 3
0.6379	Remote Similarity	NPD2570	Approved
0.6379	Remote Similarity	NPD2574	Discontinued
0.6379	Remote Similarity	NPD4745	Approved
0.6379	Remote Similarity	NPD2571	Approved
0.6378	Remote Similarity	NPD4329	Approved
0.6378	Remote Similarity	NPD4330	Approved
0.6368	Remote Similarity	NPD4499	Approved
0.6339	Remote Similarity	NPD5941	Approved
0.6339	Remote Similarity	NPD5942	Approved
0.6337	Remote Similarity	NPD766	Clinical (unspecified phase)
0.6333	Remote Similarity	NPD2820	Phase 3
0.633	Remote Similarity	NPD2427	Approved
0.6328	Remote Similarity	NPD2567	Approved
0.6328	Remote Similarity	NPD2569	Approved
0.6325	Remote Similarity	NPD2994	Approved
0.6321	Remote Similarity	NPD5727	Clinical (unspecified phase)
0.6319	Remote Similarity	NPD6416	Phase 2
0.6311	Remote Similarity	NPD7777	Approved
0.6311	Remote Similarity	NPD53	Approved
0.6311	Remote Similarity	NPD7778	Approved
0.631	Remote Similarity	NPD7105	Phase 1
0.6307	Remote Similarity	NPD4684	Phase 3
0.6307	Remote Similarity	NPD4686	Approved
0.6307	Remote Similarity	NPD4685	Phase 3
0.6302	Remote Similarity	NPD2037	Approved
0.6294	Remote Similarity	NPD6878	Phase 2
0.6294	Remote Similarity	NPD6879	Phase 2
0.628	Remote Similarity	NPD6661	Clinical (unspecified phase)
0.6278	Remote Similarity	NPD2365	Approved
0.6276	Remote Similarity	NPD3792	Approved
0.6272	Remote Similarity	NPD4775	Clinical (unspecified phase)
0.6265	Remote Similarity	NPD2115	Approved
0.6265	Remote Similarity	NPD2116	Approved
0.6265	Remote Similarity	NPD2117	Pre-registration
0.6264	Remote Similarity	NPD5931	Phase 3
0.6264	Remote Similarity	NPD5932	Phase 3
0.6264	Remote Similarity	NPD5933	Phase 3
0.6263	Remote Similarity	NPD3471	Approved
0.6263	Remote Similarity	NPD3470	Approved
0.6262	Remote Similarity	NPD3828	Approved
0.6256	Remote Similarity	NPD5504	Discontinued
0.6243	Remote Similarity	NPD7114	Clinical (unspecified phase)
0.6243	Remote Similarity	NPD5024	Approved
0.6237	Remote Similarity	NPD2432	Approved
0.6237	Remote Similarity	NPD2431	Approved
0.6232	Remote Similarity	NPD4397	Phase 1
0.6231	Remote Similarity	NPD8281	Discontinued
0.6224	Remote Similarity	NPD8022	Clinical (unspecified phase)
0.6218	Remote Similarity	NPD2455	Approved
0.6218	Remote Similarity	NPD2454	Approved
0.6216	Remote Similarity	NPD1405	Approved
0.6215	Remote Similarity	NPD1071	Clinical (unspecified phase)
0.6213	Remote Similarity	NPD2946	Phase 2
0.6205	Remote Similarity	NPD5997	Discontinued
0.6201	Remote Similarity	NPD3648	Clinical (unspecified phase)
0.6198	Remote Similarity	NPD7035	Approved
0.6198	Remote Similarity	NPD5430	Discontinued
0.6198	Remote Similarity	NPD7036	Phase 3
0.619	Remote Similarity	NPD3031	Approved
0.619	Remote Similarity	NPD3030	Approved
0.619	Remote Similarity	NPD3032	Approved
0.6186	Remote Similarity	NPD7595	Discontinued
0.618	Remote Similarity	NPD6102	Clinical (unspecified phase)
0.6179	Remote Similarity	NPD4901	Clinical (unspecified phase)
0.6167	Remote Similarity	NPD5068	Clinical (unspecified phase)
0.6162	Remote Similarity	NPD3782	Discontinued
0.6162	Remote Similarity	NPD5881	Clinical (unspecified phase)
0.6162	Remote Similarity	NPD2869	Clinical (unspecified phase)
0.615	Remote Similarity	NPD2948	Discontinued
0.6145	Remote Similarity	NPD2670	Approved
0.6142	Remote Similarity	NPD2083	Clinical (unspecified phase)
0.6138	Remote Similarity	NPD1663	Discontinued
0.6136	Remote Similarity	NPD7168	Phase 3
0.6134	Remote Similarity	NPD2404	Discontinued
0.612	Remote Similarity	NPD7488	Clinical (unspecified phase)
0.6108	Remote Similarity	NPD7683	Discontinued
0.6091	Remote Similarity	NPD5466	Approved
0.6089	Remote Similarity	NPD5725	Approved
0.6082	Remote Similarity	NPD8003	Clinical (unspecified phase)
0.6082	Remote Similarity	NPD8002	Clinical (unspecified phase)
0.6078	Remote Similarity	NPD4334	Discontinued
0.6077	Remote Similarity	NPD4987	Clinical (unspecified phase)
0.6061	Remote Similarity	NPD3978	Clinical (unspecified phase)
0.6061	Remote Similarity	NPD2607	Approved
0.6058	Remote Similarity	NPD5548	Clinical (unspecified phase)
0.6056	Remote Similarity	NPD1294	Discontinued
0.6054	Remote Similarity	NPD4041	Approved
0.6053	Remote Similarity	NPD6913	Approved
0.6051	Remote Similarity	NPD2844	Phase 3
0.605	Remote Similarity	NPD5897	Approved
0.605	Remote Similarity	NPD5899	Approved
0.605	Remote Similarity	NPD5898	Approved
0.6047	Remote Similarity	NPD2907	Approved
0.6047	Remote Similarity	NPD4082	Approved
0.6047	Remote Similarity	NPD2906	Approved
0.6047	Remote Similarity	NPD1360	Approved
0.6036	Remote Similarity	NPD3437	Discontinued
0.6033	Remote Similarity	NPD2435	Approved
0.6031	Remote Similarity	NPD7591	Clinical (unspecified phase)
0.6029	Remote Similarity	NPD6891	Phase 2
0.6029	Remote Similarity	NPD8021	Approved
0.6029	Remote Similarity	NPD8020	Approved
0.6029	Remote Similarity	NPD5195	Discontinued
0.6029	Remote Similarity	NPD5003	Discontinued
0.6028	Remote Similarity	NPD7174	Clinical (unspecified phase)
0.6023	Remote Similarity	NPD4676	Approved
0.6021	Remote Similarity	NPD8630	Approved
0.602	Remote Similarity	NPD7795	Phase 2
0.6019	Remote Similarity	NPD4370	Phase 3
0.6011	Remote Similarity	NPD6566	Discontinued
0.6011	Remote Similarity	NPD7714	Approved
0.6011	Remote Similarity	NPD7715	Approved
0.601	Remote Similarity	NPD7940	Phase 3
0.601	Remote Similarity	NPD7944	Discontinued
0.601	Remote Similarity	NPD7449	Clinical (unspecified phase)
0.601	Remote Similarity	NPD6316	Clinical (unspecified phase)
0.6	Remote Similarity	NPD7881	Approved
0.6	Remote Similarity	NPD6073	Approved
0.6	Remote Similarity	NPD8173	Phase 2
0.6	Remote Similarity	NPD5823	Approved
0.6	Remote Similarity	NPD6608	Clinical (unspecified phase)
0.6	Remote Similarity	NPD8172	Phase 2
0.6	Remote Similarity	NPD6017	Discontinued
0.5991	Remote Similarity	NPD4900	Clinical (unspecified phase)
0.5991	Remote Similarity	NPD5860	Discontinued
0.5991	Remote Similarity	NPD6238	Discontinued
0.599	Remote Similarity	NPD7570	Approved
0.599	Remote Similarity	NPD7569	Approved
0.5989	Remote Similarity	NPD989	Approved
0.5989	Remote Similarity	NPD4738	Phase 2
0.5989	Remote Similarity	NPD4432	Discontinued
0.5979	Remote Similarity	NPD3399	Approved
0.5979	Remote Similarity	NPD3790	Phase 2
0.5978	Remote Similarity	NPD6301	Phase 2
0.5977	Remote Similarity	NPD6792	Phase 3
0.5973	Remote Similarity	NPD3940	Clinical (unspecified phase)
0.5973	Remote Similarity	NPD7186	Phase 3
0.5972	Remote Similarity	NPD7666	Phase 3
0.5972	Remote Similarity	NPD7665	Phase 2
0.5972	Remote Similarity	NPD6874	Approved
0.5969	Remote Similarity	NPD3468	Approved

Bioactivity similarity: Similar Natural Products in NPASS

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

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

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data