NPASS Compound

Structure

CID57036 OpenBabel06191715392D 23 27 0 0 1 0 0 0 0 0999 V2000 4.2360 -1.3926 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1973 3.6668 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9927 4.1252 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4062 0.9107 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5991 2.2802 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6057 2.2761 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6196 -0.4943 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9139 -0.0961 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1925 2.7393 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5950 1.3649 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4184 -0.0189 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7985 2.7424 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8084 -0.0401 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6048 1.3584 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9883 2.2798 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7961 0.8895 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9955 1.3517 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1911 0.8989 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7885 3.6658 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.0152 -0.5121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2238 -0.4698 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2877 0.7435 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 21 1 0 0 0 0 2 3 1 0 0 0 0 2 9 1 0 0 0 0 3 19 1 0 0 0 0 4 10 2 0 0 0 0 4 11 1 0 0 0 0 5 10 1 0 0 0 0 6 9 2 0 0 0 0 6 14 1 0 0 0 0 7 11 2 0 0 0 0 7 13 1 0 0 0 0 8 22 1 0 0 0 0 8 23 1 0 0 0 0 9 15 1 0 0 0 0 10 16 1 0 0 0 0 11 21 1 0 0 0 0 12 5 1 1 0 0 0 12 15 1 0 0 0 0 12 19 1 0 0 0 0 13 16 2 0 0 0 0 13 20 1 0 0 0 0 14 18 2 0 0 0 0 14 22 1 0 0 0 0 15 17 2 0 0 0 0 16 17 1 0 0 0 0 17 18 1 0 0 0 0 18 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	311.12
Volume:	307.441
LogP:	2.882
LogD:	2.788
LogS:	-2.84
# Rotatable Bonds:	1
TPSA:	59.95
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	5
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.847
Synthetic Accessibility Score:	3.345
Fsp3:	0.333
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:	-5.24
MDCK Permeability:	1.5419804185512476e-05
Pgp-inhibitor:	0.015
Pgp-substrate:	0.815
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.727
Plasma Protein Binding (PPB):	90.26395416259766%
Volume Distribution (VD):	2.244
Pgp-substrate:	7.368967056274414%

ADMET: Metabolism

CYP1A2-inhibitor:	0.874
CYP1A2-substrate:	0.608
CYP2C19-inhibitor:	0.314
CYP2C19-substrate:	0.675
CYP2C9-inhibitor:	0.015
CYP2C9-substrate:	0.7
CYP2D6-inhibitor:	0.751
CYP2D6-substrate:	0.919
CYP3A4-inhibitor:	0.455
CYP3A4-substrate:	0.55

ADMET: Excretion

Clearance (CL):	13.745
Half-life (T1/2):	0.197

ADMET: Toxicity

hERG Blockers:	0.623
Human Hepatotoxicity (H-HT):	0.42
Drug-inuced Liver Injury (DILI):	0.618
AMES Toxicity:	0.828
Rat Oral Acute Toxicity:	0.739
Maximum Recommended Daily Dose:	0.983
Skin Sensitization:	0.473
Carcinogencity:	0.246
Eye Corrosion:	0.003
Eye Irritation:	0.01
Respiratory Toxicity:	0.943

Download Data

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

Natural Product: NPC57036

Natural Product ID:	NPC57036
*Common Name:**	Calycinine
IUPAC Name:	n.a.
Synonyms:	Calycinine
Standard InCHIKey:	PTEWWARRGIJHQK-LBPRGKRZSA-N
Standard InCHI:	InChI=1S/C18H17NO4/c1-21-11-4-10-5-12-15-9(2-3-19-12)6-14-18(23-8-22-14)17(15)16(10)13(20)7-11/h4,6-7,12,19-20H,2-3,5,8H2,1H3/t12-/m0/s1
SMILES:	COc1cc2C[C@@H]3NCCc4c3c(c2c(c1)O)c1OCOc1c4
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL226824
PubChem CID:	44422610
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0000381] Aporphines

*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
NPO18509	Fissistigma oldhamii	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10978218]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	seeds	n.a.	n.a.	PMID[11141125]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12398544]
NPO18509	Fissistigma oldhamii	Species	Annonaceae	Eukaryota	stem	n.a.	n.a.	PMID[17081761]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18419154]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19296389]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21910504]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	seeds	n.a.	n.a.	PMID[22011319]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	seed	n.a.	PMID[22011319]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	Barks	n.a.	n.a.	PMID[2348205]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	fruit	n.a.	PMID[8786370]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	bark	n.a.	n.a.	PMID[9214729]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18509	Fissistigma oldhamii	Species	Annonaceae	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	2
Others	3

Activity Type	# Activity
Cell Line	1
Others	4

Target ID	Target Type	Target Name	Activity Type	Activity Relation	Value	Unit	Reference
NPT1076	Cell Line	B-cells	IC50	=	2930.0	nM	PMID[523739]
NPT27	Others	Unspecified	CC50	=	316000.0	nM	PMID[523739]
NPT2	Others	Unspecified	IC50	=	4860.0	nM	PMID[523739]
NPT2	Others	Unspecified	Ratio CC50/IC50	=	65.0	n.a.	PMID[523739]
NPT2	Others	Unspecified	Ratio CC50/IC50	=	108.0	n.a.	PMID[523739]

☑ 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 NPC57036 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	357
0.1-0.2	1857
0.2-0.3	8206
0.3-0.4	9993
0.4-0.5	5957
0.5-0.6	10868
0.6-0.7	4407
0.7-0.8	735
0.8-0.85	212
0.85-0.9	65
0.9-0.95	31
0.95-1	9

Similarity Score	Similarity Level	Natural Product ID
0.9822	High Similarity	NPC476576
0.9822	High Similarity	NPC186546
0.9701	High Similarity	NPC258695
0.9701	High Similarity	NPC470879
0.9643	High Similarity	NPC32413
0.9643	High Similarity	NPC474506
0.9529	High Similarity	NPC135772
0.9527	High Similarity	NPC155442
0.9527	High Similarity	NPC476574
0.9527	High Similarity	NPC312918
0.9527	High Similarity	NPC477561
0.9524	High Similarity	NPC23219
0.9464	High Similarity	NPC112575
0.9425	High Similarity	NPC117717
0.9405	High Similarity	NPC477558
0.9353	High Similarity	NPC474507
0.9341	High Similarity	NPC6152
0.9286	High Similarity	NPC149090
0.9286	High Similarity	NPC19520
0.9235	High Similarity	NPC476577
0.9235	High Similarity	NPC148709
0.9235	High Similarity	NPC173416
0.9226	High Similarity	NPC152212
0.9222	High Similarity	NPC204947
0.92	High Similarity	NPC82763
0.9181	High Similarity	NPC320223
0.9181	High Similarity	NPC114364
0.9176	High Similarity	NPC199465
0.9176	High Similarity	NPC128560
0.9176	High Similarity	NPC229166
0.9118	High Similarity	NPC477020
0.9118	High Similarity	NPC192135
0.9118	High Similarity	NPC66341
0.9112	High Similarity	NPC69712
0.9112	High Similarity	NPC26240
0.9112	High Similarity	NPC477562
0.9086	High Similarity	NPC214116
0.9059	High Similarity	NPC239775
0.9048	High Similarity	NPC86144
0.9048	High Similarity	NPC304659
0.9023	High Similarity	NPC476575
0.8994	High Similarity	NPC298979
0.8994	High Similarity	NPC247389
0.8988	High Similarity	NPC167546
0.8988	High Similarity	NPC16805
0.8988	High Similarity	NPC302527
0.8935	High Similarity	NPC476432
0.8935	High Similarity	NPC24264
0.8935	High Similarity	NPC219341
0.8933	High Similarity	NPC475754
0.8929	High Similarity	NPC189470
0.8914	High Similarity	NPC116284
0.8914	High Similarity	NPC248642
0.8908	High Similarity	NPC267408
0.8889	High Similarity	NPC118274
0.8889	High Similarity	NPC168753
0.8882	High Similarity	NPC210918
0.8876	High Similarity	NPC225774
0.8864	High Similarity	NPC156576
0.8824	High Similarity	NPC81247
0.8824	High Similarity	NPC476573
0.8824	High Similarity	NPC35627
0.8824	High Similarity	NPC46990
0.8807	High Similarity	NPC275132
0.88	High Similarity	NPC126284
0.8772	High Similarity	NPC81218
0.8772	High Similarity	NPC145832
0.8772	High Similarity	NPC117188
0.8772	High Similarity	NPC306555
0.8772	High Similarity	NPC158376
0.8772	High Similarity	NPC12053
0.8772	High Similarity	NPC474931
0.8772	High Similarity	NPC205421
0.8765	High Similarity	NPC306843
0.8765	High Similarity	NPC196447
0.8765	High Similarity	NPC212794
0.8765	High Similarity	NPC253043
0.8765	High Similarity	NPC96603
0.8765	High Similarity	NPC13504
0.8765	High Similarity	NPC477563
0.8765	High Similarity	NPC78222
0.8765	High Similarity	NPC136508
0.8713	High Similarity	NPC223077
0.8713	High Similarity	NPC193853
0.8713	High Similarity	NPC56887
0.8706	High Similarity	NPC324144
0.8698	High Similarity	NPC306902
0.8698	High Similarity	NPC232924
0.8698	High Similarity	NPC160298
0.8698	High Similarity	NPC477559
0.8698	High Similarity	NPC266753
0.8655	High Similarity	NPC209377
0.8631	High Similarity	NPC203784
0.8631	High Similarity	NPC170503
0.8631	High Similarity	NPC126519
0.8596	High Similarity	NPC1229
0.858	High Similarity	NPC476572
0.8571	High Similarity	NPC99659
0.8571	High Similarity	NPC325871
0.8531	High Similarity	NPC118633
0.8531	High Similarity	NPC294790
0.8531	High Similarity	NPC148693
0.8525	High Similarity	NPC256124
0.8497	Intermediate Similarity	NPC195392
0.848	Intermediate Similarity	NPC27410
0.848	Intermediate Similarity	NPC166014
0.8462	Intermediate Similarity	NPC281581
0.8439	Intermediate Similarity	NPC24465
0.843	Intermediate Similarity	NPC79402
0.843	Intermediate Similarity	NPC80759
0.8421	Intermediate Similarity	NPC7393
0.8418	Intermediate Similarity	NPC329969
0.84	Intermediate Similarity	NPC241055
0.8391	Intermediate Similarity	NPC13916
0.8391	Intermediate Similarity	NPC264850
0.8372	Intermediate Similarity	NPC119649
0.8372	Intermediate Similarity	NPC235143
0.8372	Intermediate Similarity	NPC205255
0.8372	Intermediate Similarity	NPC230956
0.8372	Intermediate Similarity	NPC271388
0.837	Intermediate Similarity	NPC24260
0.837	Intermediate Similarity	NPC478093
0.8363	Intermediate Similarity	NPC79328
0.8362	Intermediate Similarity	NPC2314
0.8333	Intermediate Similarity	NPC257269
0.8333	Intermediate Similarity	NPC232514
0.8333	Intermediate Similarity	NPC168409
0.8333	Intermediate Similarity	NPC276944
0.8333	Intermediate Similarity	NPC238530
0.8324	Intermediate Similarity	NPC473589
0.8324	Intermediate Similarity	NPC30182
0.8324	Intermediate Similarity	NPC478092
0.8324	Intermediate Similarity	NPC478091
0.8314	Intermediate Similarity	NPC111485
0.8314	Intermediate Similarity	NPC221864
0.8305	Intermediate Similarity	NPC231371
0.8304	Intermediate Similarity	NPC29647
0.8297	Intermediate Similarity	NPC16357
0.8297	Intermediate Similarity	NPC95426
0.8297	Intermediate Similarity	NPC9867
0.8297	Intermediate Similarity	NPC302245
0.8286	Intermediate Similarity	NPC68328
0.8284	Intermediate Similarity	NPC81733
0.8284	Intermediate Similarity	NPC326316
0.8278	Intermediate Similarity	NPC119068
0.8278	Intermediate Similarity	NPC40496
0.8274	Intermediate Similarity	NPC60538
0.8274	Intermediate Similarity	NPC207824
0.8261	Intermediate Similarity	NPC11296
0.8261	Intermediate Similarity	NPC274661
0.8261	Intermediate Similarity	NPC175890
0.8261	Intermediate Similarity	NPC82457
0.8261	Intermediate Similarity	NPC48490
0.8258	Intermediate Similarity	NPC474051
0.8251	Intermediate Similarity	NPC139783
0.8251	Intermediate Similarity	NPC65312
0.8235	Intermediate Similarity	NPC114124
0.8232	Intermediate Similarity	NPC230276
0.8218	Intermediate Similarity	NPC60186
0.8216	Intermediate Similarity	NPC191132
0.8216	Intermediate Similarity	NPC60295
0.8212	Intermediate Similarity	NPC187678
0.8207	Intermediate Similarity	NPC275680
0.8207	Intermediate Similarity	NPC474904
0.8207	Intermediate Similarity	NPC22115
0.8207	Intermediate Similarity	NPC237579
0.8192	Intermediate Similarity	NPC204908
0.8192	Intermediate Similarity	NPC83198
0.8187	Intermediate Similarity	NPC477564
0.8187	Intermediate Similarity	NPC299990
0.8187	Intermediate Similarity	NPC73492
0.8187	Intermediate Similarity	NPC2295
0.8177	Intermediate Similarity	NPC244554
0.8176	Intermediate Similarity	NPC76213
0.8176	Intermediate Similarity	NPC277669
0.8156	Intermediate Similarity	NPC232386
0.8156	Intermediate Similarity	NPC152680
0.8156	Intermediate Similarity	NPC190783
0.8152	Intermediate Similarity	NPC47077
0.8152	Intermediate Similarity	NPC14507
0.8146	Intermediate Similarity	NPC75958
0.8142	Intermediate Similarity	NPC302275
0.814	Intermediate Similarity	NPC41178
0.814	Intermediate Similarity	NPC244112
0.814	Intermediate Similarity	NPC138487
0.814	Intermediate Similarity	NPC216459
0.8136	Intermediate Similarity	NPC150879
0.8125	Intermediate Similarity	NPC180306
0.8108	Intermediate Similarity	NPC312531
0.8107	Intermediate Similarity	NPC475959
0.8107	Intermediate Similarity	NPC37144
0.8107	Intermediate Similarity	NPC59907
0.8105	Intermediate Similarity	NPC475654
0.8092	Intermediate Similarity	NPC146288
0.8092	Intermediate Similarity	NPC186063
0.8087	Intermediate Similarity	NPC233718
0.8085	Intermediate Similarity	NPC162653
0.8077	Intermediate Similarity	NPC243454
0.8077	Intermediate Similarity	NPC475479
0.8045	Intermediate Similarity	NPC109925

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 NPC57036 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	199
0.1-0.2	742
0.2-0.3	1199
0.3-0.4	2308
0.4-0.5	2635
0.5-0.6	1427
0.6-0.7	536
0.7-0.8	102
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8278	Intermediate Similarity	NPD8453	Clinical (unspecified phase)
0.7989	Intermediate Similarity	NPD8054	Approved
0.7989	Intermediate Similarity	NPD8053	Approved
0.7957	Intermediate Similarity	NPD7906	Approved
0.7929	Intermediate Similarity	NPD7827	Phase 1
0.7886	Intermediate Similarity	NPD2978	Approved
0.7886	Intermediate Similarity	NPD2977	Approved
0.7877	Intermediate Similarity	NPD3051	Approved
0.7838	Intermediate Similarity	NPD4577	Approved
0.7838	Intermediate Similarity	NPD4578	Approved
0.7833	Intermediate Similarity	NPD2969	Approved
0.7833	Intermediate Similarity	NPD2970	Approved
0.7807	Intermediate Similarity	NPD4663	Approved
0.7802	Intermediate Similarity	NPD8099	Discontinued
0.7802	Intermediate Similarity	NPD8251	Approved
0.7802	Intermediate Similarity	NPD8252	Approved
0.779	Intermediate Similarity	NPD27	Approved
0.779	Intermediate Similarity	NPD2489	Approved
0.7778	Intermediate Similarity	NPD2421	Approved
0.7778	Intermediate Similarity	NPD2420	Approved
0.776	Intermediate Similarity	NPD8156	Discontinued
0.7742	Intermediate Similarity	NPD7313	Approved
0.7742	Intermediate Similarity	NPD7311	Approved
0.7742	Intermediate Similarity	NPD7312	Approved
0.7742	Intermediate Similarity	NPD7310	Approved
0.7733	Intermediate Similarity	NPD4584	Approved
0.7727	Intermediate Similarity	NPD7298	Approved
0.7719	Intermediate Similarity	NPD3845	Phase 1
0.7719	Intermediate Similarity	NPD2422	Clinical (unspecified phase)
0.7701	Intermediate Similarity	NPD7309	Approved
0.7697	Intermediate Similarity	NPD6788	Approved
0.7692	Intermediate Similarity	NPD4664	Clinical (unspecified phase)
0.768	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.763	Intermediate Similarity	NPD1424	Approved
0.7598	Intermediate Similarity	NPD4581	Clinical (unspecified phase)
0.7596	Intermediate Similarity	NPD4481	Phase 3
0.7543	Intermediate Similarity	NPD6031	Approved
0.7543	Intermediate Similarity	NPD6030	Approved
0.7543	Intermediate Similarity	NPD4727	Phase 1
0.7513	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.7512	Intermediate Similarity	NPD6723	Discontinued
0.7486	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.7475	Intermediate Similarity	NPD5006	Approved
0.7475	Intermediate Similarity	NPD5005	Approved
0.7459	Intermediate Similarity	NPD4055	Discovery
0.7457	Intermediate Similarity	NPD5084	Clinical (unspecified phase)
0.743	Intermediate Similarity	NPD3383	Approved
0.743	Intermediate Similarity	NPD3382	Approved
0.743	Intermediate Similarity	NPD3384	Approved
0.7424	Intermediate Similarity	NPD3452	Approved
0.7424	Intermediate Similarity	NPD3450	Approved
0.7424	Intermediate Similarity	NPD2493	Approved
0.7424	Intermediate Similarity	NPD2494	Approved
0.7405	Intermediate Similarity	NPD2898	Approved
0.7398	Intermediate Similarity	NPD2975	Approved
0.7398	Intermediate Similarity	NPD2974	Approved
0.7398	Intermediate Similarity	NPD2973	Approved
0.7391	Intermediate Similarity	NPD6071	Discontinued
0.7389	Intermediate Similarity	NPD4585	Approved
0.7377	Intermediate Similarity	NPD7201	Clinical (unspecified phase)
0.7363	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.7363	Intermediate Similarity	NPD7831	Phase 2
0.7363	Intermediate Similarity	NPD7833	Phase 2
0.736	Intermediate Similarity	NPD4420	Approved
0.7356	Intermediate Similarity	NPD5241	Discontinued
0.7348	Intermediate Similarity	NPD2563	Approved
0.7348	Intermediate Similarity	NPD2560	Approved
0.7341	Intermediate Similarity	NPD3060	Approved
0.7321	Intermediate Similarity	NPD554	Clinical (unspecified phase)
0.732	Intermediate Similarity	NPD2488	Approved
0.732	Intermediate Similarity	NPD2490	Approved
0.7313	Intermediate Similarity	NPD4583	Approved
0.7313	Intermediate Similarity	NPD4582	Approved
0.7309	Intermediate Similarity	NPD8152	Approved
0.7309	Intermediate Similarity	NPD8153	Approved
0.7302	Intermediate Similarity	NPD6297	Approved
0.7297	Intermediate Similarity	NPD4010	Discontinued
0.7292	Intermediate Similarity	NPD5087	Clinical (unspecified phase)
0.7287	Intermediate Similarity	NPD42	Phase 2
0.7287	Intermediate Similarity	NPD6042	Phase 2
0.7286	Intermediate Similarity	NPD4580	Approved
0.7267	Intermediate Similarity	NPD1632	Clinical (unspecified phase)
0.7264	Intermediate Similarity	NPD4002	Approved
0.7264	Intermediate Similarity	NPD4004	Approved
0.7263	Intermediate Similarity	NPD4005	Discontinued
0.7263	Intermediate Similarity	NPD7261	Clinical (unspecified phase)
0.7257	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7247	Intermediate Similarity	NPD5976	Discontinued
0.7228	Intermediate Similarity	NPD5709	Phase 3
0.7216	Intermediate Similarity	NPD6783	Clinical (unspecified phase)
0.7191	Intermediate Similarity	NPD3647	Clinical (unspecified phase)
0.7189	Intermediate Similarity	NPD4666	Phase 3
0.7188	Intermediate Similarity	NPD2971	Approved
0.7188	Intermediate Similarity	NPD2968	Approved
0.7182	Intermediate Similarity	NPD4773	Phase 2
0.7182	Intermediate Similarity	NPD4772	Phase 2
0.7174	Intermediate Similarity	NPD7975	Clinical (unspecified phase)
0.7174	Intermediate Similarity	NPD5604	Discontinued
0.7167	Intermediate Similarity	NPD4017	Approved
0.7151	Intermediate Similarity	NPD6107	Approved
0.715	Intermediate Similarity	NPD6853	Approved
0.715	Intermediate Similarity	NPD6851	Approved
0.7143	Intermediate Similarity	NPD37	Approved
0.7129	Intermediate Similarity	NPD7047	Phase 3
0.7122	Intermediate Similarity	NPD4859	Phase 1
0.7112	Intermediate Similarity	NPD4166	Phase 2
0.7098	Intermediate Similarity	NPD3534	Clinical (unspecified phase)
0.7089	Intermediate Similarity	NPD6997	Phase 2
0.7085	Intermediate Similarity	NPD7667	Clinical (unspecified phase)
0.7065	Intermediate Similarity	NPD8095	Phase 1
0.7059	Intermediate Similarity	NPD4040	Phase 1
0.7056	Intermediate Similarity	NPD3640	Phase 3
0.7056	Intermediate Similarity	NPD3639	Approved
0.7056	Intermediate Similarity	NPD3641	Approved
0.7047	Intermediate Similarity	NPD7549	Discontinued
0.7045	Intermediate Similarity	NPD5177	Phase 3
0.7043	Intermediate Similarity	NPD6234	Discontinued
0.7029	Intermediate Similarity	NPD2029	Clinical (unspecified phase)
0.7027	Intermediate Similarity	NPD4967	Phase 2
0.7027	Intermediate Similarity	NPD4965	Approved
0.7027	Intermediate Similarity	NPD4966	Approved
0.7022	Intermediate Similarity	NPD7124	Phase 2
0.7005	Intermediate Similarity	NPD5677	Discontinued
0.6994	Remote Similarity	NPD2568	Approved
0.6983	Remote Similarity	NPD7598	Phase 2
0.6979	Remote Similarity	NPD7479	Phase 2
0.6977	Remote Similarity	NPD3109	Approved
0.6977	Remote Similarity	NPD3110	Approved
0.6966	Remote Similarity	NPD5160	Discontinued
0.6963	Remote Similarity	NPD8155	Clinical (unspecified phase)
0.6963	Remote Similarity	NPD7228	Approved
0.6954	Remote Similarity	NPD7243	Clinical (unspecified phase)
0.6944	Remote Similarity	NPD7447	Phase 1
0.6944	Remote Similarity	NPD1754	Clinical (unspecified phase)
0.6944	Remote Similarity	NPD4160	Clinical (unspecified phase)
0.6943	Remote Similarity	NPD6996	Clinical (unspecified phase)
0.694	Remote Similarity	NPD4678	Approved
0.694	Remote Similarity	NPD4675	Approved
0.6927	Remote Similarity	NPD4873	Discontinued
0.6923	Remote Similarity	NPD7281	Phase 3
0.6923	Remote Similarity	NPD7280	Phase 3
0.6915	Remote Similarity	NPD5582	Discontinued
0.6914	Remote Similarity	NPD6029	Clinical (unspecified phase)
0.6914	Remote Similarity	NPD6028	Clinical (unspecified phase)
0.691	Remote Similarity	NPD3977	Clinical (unspecified phase)
0.6906	Remote Similarity	NPD5261	Clinical (unspecified phase)
0.6906	Remote Similarity	NPD6090	Discontinued
0.6902	Remote Similarity	NPD5089	Approved
0.6902	Remote Similarity	NPD5090	Approved
0.6901	Remote Similarity	NPD2669	Clinical (unspecified phase)
0.6893	Remote Similarity	NPD4257	Approved
0.6893	Remote Similarity	NPD4256	Phase 2
0.6889	Remote Similarity	NPD7213	Phase 3
0.6889	Remote Similarity	NPD7212	Phase 2
0.6885	Remote Similarity	NPD6523	Clinical (unspecified phase)
0.6878	Remote Similarity	NPD6625	Approved
0.6872	Remote Similarity	NPD2677	Approved
0.6869	Remote Similarity	NPD6842	Approved
0.6869	Remote Similarity	NPD6841	Approved
0.6869	Remote Similarity	NPD6843	Phase 3
0.6869	Remote Similarity	NPD8318	Clinical (unspecified phase)
0.6863	Remote Similarity	NPD6612	Phase 2
0.6854	Remote Similarity	NPD4162	Approved
0.6854	Remote Similarity	NPD6674	Discontinued
0.6851	Remote Similarity	NPD3157	Approved
0.6851	Remote Similarity	NPD3158	Phase 1
0.6834	Remote Similarity	NPD3408	Clinical (unspecified phase)
0.6831	Remote Similarity	NPD3686	Approved
0.6831	Remote Similarity	NPD3687	Approved
0.6827	Remote Similarity	NPD7584	Approved
0.6823	Remote Similarity	NPD5602	Clinical (unspecified phase)
0.6821	Remote Similarity	NPD7038	Approved
0.6821	Remote Similarity	NPD7039	Approved
0.682	Remote Similarity	NPD5619	Clinical (unspecified phase)
0.6818	Remote Similarity	NPD1753	Discontinued
0.6818	Remote Similarity	NPD4108	Discontinued
0.6816	Remote Similarity	NPD5754	Discontinued
0.6811	Remote Similarity	NPD6072	Discontinued
0.6806	Remote Similarity	NPD4083	Discontinued
0.6806	Remote Similarity	NPD7907	Approved
0.6802	Remote Similarity	NPD5155	Approved
0.6802	Remote Similarity	NPD5156	Approved
0.6802	Remote Similarity	NPD7922	Phase 1
0.68	Remote Similarity	NPD817	Approved
0.68	Remote Similarity	NPD823	Approved
0.6796	Remote Similarity	NPD3515	Approved
0.6796	Remote Similarity	NPD3516	Approved
0.6796	Remote Similarity	NPD3057	Approved
0.6789	Remote Similarity	NPD7802	Discontinued
0.6784	Remote Similarity	NPD3349	Phase 2
0.678	Remote Similarity	NPD5457	Discontinued
0.6765	Remote Similarity	NPD3055	Approved
0.6765	Remote Similarity	NPD3053	Approved
0.6763	Remote Similarity	NPD5718	Phase 2
0.6761	Remote Similarity	NPD7930	Approved
0.676	Remote Similarity	NPD4237	Approved
0.676	Remote Similarity	NPD4236	Phase 3
0.6754	Remote Similarity	NPD4606	Clinical (unspecified phase)
0.6753	Remote Similarity	NPD5096	Phase 3
0.6753	Remote Similarity	NPD5095	Phase 3

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