NPASS Compound

Structure

NPC288149 OpenBabel07101718332D 29 34 0 0 1 0 0 0 0 0999 V2000 4.6665 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5296 -4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3956 -4.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3956 -2.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2024 -4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9945 -0.1045 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8005 -3.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2709 -5.6654 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5296 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2024 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2024 -1.0827 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2617 -4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2617 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0685 -4.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3364 -2.5827 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3364 -1.5827 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0685 -2.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0685 -1.5827 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9345 -4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9345 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4067 -0.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9345 -1.0827 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3849 -1.1215 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8005 -2.5827 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 -3.2127 -4.3917 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2127 -2.7737 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2764 -5.5608 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6776 -4.7518 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 24 1 0 0 0 0 2 3 2 0 0 0 0 2 9 1 0 0 0 0 3 12 1 0 0 0 0 4 9 2 0 0 0 0 4 13 1 0 0 0 0 5 10 2 0 0 0 0 5 14 1 0 0 0 0 6 25 1 0 0 0 0 7 26 1 0 0 0 0 7 27 1 0 0 0 0 8 28 1 0 0 0 0 8 29 1 0 0 0 0 10 15 1 0 0 0 0 10 17 1 0 0 0 0 11 6 1 6 0 0 0 11 16 1 0 0 0 0 11 18 1 0 0 0 0 12 13 2 0 0 0 0 12 26 1 0 0 0 0 13 27 1 0 0 0 0 14 19 2 0 0 0 0 14 28 1 0 0 0 0 15 9 1 1 0 0 0 15 16 1 0 0 0 0 16 21 1 1 0 0 0 17 18 1 0 0 0 0 17 20 2 0 0 0 0 18 22 1 1 0 0 0 19 20 1 0 0 0 0 19 29 1 0 0 0 0 20 24 1 0 0 0 0 21 23 2 0 0 0 0 21 25 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	398.1
Volume:	372.3
LogP:	1.419
LogD:	1.676
LogS:	-3.759
# Rotatable Bonds:	2
TPSA:	92.68
# H-Bond Aceptor:	8
# H-Bond Donor:	1
# Rings:	6
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.769
Synthetic Accessibility Score:	3.985
Fsp3:	0.381
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.878
MDCK Permeability:	3.714452395797707e-05
Pgp-inhibitor:	0.775
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.001
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.004

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.11
Plasma Protein Binding (PPB):	96.70474243164062%
Volume Distribution (VD):	1.527
Pgp-substrate:	1.9563097953796387%

ADMET: Metabolism

CYP1A2-inhibitor:	0.335
CYP1A2-substrate:	0.87
CYP2C19-inhibitor:	0.96
CYP2C19-substrate:	0.847
CYP2C9-inhibitor:	0.773
CYP2C9-substrate:	0.894
CYP2D6-inhibitor:	0.869
CYP2D6-substrate:	0.258
CYP3A4-inhibitor:	0.956
CYP3A4-substrate:	0.798

ADMET: Excretion

Clearance (CL):	6.968
Half-life (T1/2):	0.147

ADMET: Toxicity

hERG Blockers:	0.122
Human Hepatotoxicity (H-HT):	0.215
Drug-inuced Liver Injury (DILI):	0.447
AMES Toxicity:	0.075
Rat Oral Acute Toxicity:	0.095
Maximum Recommended Daily Dose:	0.947
Skin Sensitization:	0.053
Carcinogencity:	0.522
Eye Corrosion:	0.003
Eye Irritation:	0.084
Respiratory Toxicity:	0.625

Download Data

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

Natural Product: NPC288149

Natural Product ID:	NPC288149
*Common Name:**	Cleistantoxin
IUPAC Name:	(5R,5aR,8aR,9R)-9-(1,3-benzodioxol-5-yl)-5-hydroxy-4-methoxy-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
Synonyms:	Cleistantoxin
Standard InCHIKey:	GTFKUBXSHHHPRX-QOQPWIFLSA-N
Standard InCHI:	InChI=1S/C21H18O8/c1-24-20-17-10(5-14-19(20)29-8-28-14)15(16-11(18(17)22)6-25-21(16)23)9-2-3-12-13(4-9)27-7-26-12/h2-5,11,15-16,18,22H,6-8H2,1H3/t11-,15+,16-,18+/m0/s1
SMILES:	COc1c2[C@H](O)[C@H]3COC(=O)[C@@H]3[C@@H](c2cc2c1OCO2)c1ccc2c(c1)OCO2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2146936
PubChem CID:	71452884
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001510] Lignan lactones

*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
NPO7890	Cleistanthus indochinensis	Species	Phyllanthaceae	Eukaryota	fruits	n.a.	n.a.	PMID[22938151]
NPO7890	Cleistanthus indochinensis	Species	Phyllanthaceae	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	4

Activity Type	# Activity
Cell Line	3
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	IC50	=	22.0	nM	PMID[505861]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	36.0	nM	PMID[505861]
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	35.0	nM	PMID[505861]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	14.0	nM	PMID[505861]

☑ 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 NPC288149 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	338
0.1-0.2	1326
0.2-0.3	2948
0.3-0.4	6510
0.4-0.5	10948
0.5-0.6	5406
0.6-0.7	6974
0.7-0.8	7517
0.8-0.85	545
0.85-0.9	139
0.9-0.95	40
0.95-1	6

Similarity Score	Similarity Level	Natural Product ID
0.9934	High Similarity	NPC96593
0.9803	High Similarity	NPC19947
0.9803	High Similarity	NPC207584
0.9737	High Similarity	NPC237946
0.9737	High Similarity	NPC32373
0.9548	High Similarity	NPC91634
0.9548	High Similarity	NPC268718
0.9548	High Similarity	NPC150943
0.9548	High Similarity	NPC119910
0.9539	High Similarity	NPC245948
0.9419	High Similarity	NPC181168
0.9419	High Similarity	NPC115281
0.9419	High Similarity	NPC163527
0.9408	High Similarity	NPC210642
0.9408	High Similarity	NPC13985
0.9367	High Similarity	NPC116759
0.9367	High Similarity	NPC14294
0.9363	High Similarity	NPC100465
0.9363	High Similarity	NPC152424
0.9351	High Similarity	NPC273578
0.9342	High Similarity	NPC149505
0.9308	High Similarity	NPC222531
0.9276	High Similarity	NPC177476
0.9276	High Similarity	NPC262455
0.9241	High Similarity	NPC115624
0.9226	High Similarity	NPC30009
0.9226	High Similarity	NPC103197
0.9221	High Similarity	NPC56184
0.9193	High Similarity	NPC185498
0.9161	High Similarity	NPC178574
0.9161	High Similarity	NPC65591
0.9156	High Similarity	NPC164082
0.9145	High Similarity	NPC80230
0.9145	High Similarity	NPC304687
0.9145	High Similarity	NPC65574
0.9145	High Similarity	NPC104024
0.9145	High Similarity	NPC101755
0.913	High Similarity	NPC306475
0.908	High Similarity	NPC179240
0.9079	High Similarity	NPC3982
0.9057	High Similarity	NPC470637
0.9032	High Similarity	NPC303519
0.9026	High Similarity	NPC477698
0.9012	High Similarity	NPC174734
0.9012	High Similarity	NPC474042
0.8981	High Similarity	NPC136757
0.8968	High Similarity	NPC473989
0.8968	High Similarity	NPC24425
0.8961	High Similarity	NPC304821
0.8947	High Similarity	NPC177644
0.8947	High Similarity	NPC218841
0.8947	High Similarity	NPC166884
0.8947	High Similarity	NPC191158
0.8947	High Similarity	NPC477701
0.8947	High Similarity	NPC92693
0.8947	High Similarity	NPC141569
0.8903	High Similarity	NPC293757
0.8903	High Similarity	NPC174512
0.8903	High Similarity	NPC668
0.8903	High Similarity	NPC477695
0.8903	High Similarity	NPC216223
0.8903	High Similarity	NPC474965
0.8903	High Similarity	NPC145569
0.8902	High Similarity	NPC117911
0.8861	High Similarity	NPC178195
0.8861	High Similarity	NPC312763
0.8861	High Similarity	NPC348849
0.8855	High Similarity	NPC184624
0.8854	High Similarity	NPC477699
0.8841	High Similarity	NPC79322
0.8839	High Similarity	NPC316676
0.8839	High Similarity	NPC325720
0.8831	High Similarity	NPC193779
0.8827	High Similarity	NPC198796
0.8827	High Similarity	NPC22130
0.8827	High Similarity	NPC116838
0.882	High Similarity	NPC474770
0.8816	High Similarity	NPC151423
0.8816	High Similarity	NPC40237
0.8816	High Similarity	NPC287124
0.8816	High Similarity	NPC176586
0.8816	High Similarity	NPC210354
0.8805	High Similarity	NPC186316
0.8805	High Similarity	NPC238834
0.879	High Similarity	NPC477700
0.8765	High Similarity	NPC258322
0.8765	High Similarity	NPC191352
0.8758	High Similarity	NPC474288
0.8758	High Similarity	NPC474043
0.875	High Similarity	NPC246474
0.875	High Similarity	NPC162851
0.875	High Similarity	NPC23593
0.875	High Similarity	NPC218092
0.875	High Similarity	NPC196771
0.8742	High Similarity	NPC473425
0.8727	High Similarity	NPC311912
0.8718	High Similarity	NPC262804
0.8718	High Similarity	NPC40654
0.871	High Similarity	NPC33832
0.871	High Similarity	NPC212890
0.8701	High Similarity	NPC475000
0.8698	High Similarity	NPC35266
0.8696	High Similarity	NPC19600
0.869	High Similarity	NPC107739
0.8684	High Similarity	NPC46591
0.8683	High Similarity	NPC471921
0.8683	High Similarity	NPC20114
0.8683	High Similarity	NPC312006
0.8683	High Similarity	NPC471922
0.8683	High Similarity	NPC129930
0.8683	High Similarity	NPC471920
0.8683	High Similarity	NPC474075
0.8683	High Similarity	NPC114550
0.8683	High Similarity	NPC292712
0.8679	High Similarity	NPC473236
0.8679	High Similarity	NPC24562
0.8679	High Similarity	NPC474606
0.8675	High Similarity	NPC88557
0.8671	High Similarity	NPC32079
0.8671	High Similarity	NPC475756
0.8667	High Similarity	NPC320471
0.8667	High Similarity	NPC83049
0.8667	High Similarity	NPC118162
0.8663	High Similarity	NPC470642
0.8662	High Similarity	NPC125570
0.8659	High Similarity	NPC475865
0.8647	High Similarity	NPC236089
0.8645	High Similarity	NPC475868
0.8645	High Similarity	NPC477702
0.8642	High Similarity	NPC241600
0.8642	High Similarity	NPC173726
0.8639	High Similarity	NPC263955
0.8634	High Similarity	NPC239113
0.8634	High Similarity	NPC473900
0.8634	High Similarity	NPC478055
0.8634	High Similarity	NPC115123
0.8625	High Similarity	NPC198461
0.8616	High Similarity	NPC476434
0.8616	High Similarity	NPC471154
0.8616	High Similarity	NPC302610
0.8614	High Similarity	NPC471180
0.8608	High Similarity	NPC158635
0.8608	High Similarity	NPC229882
0.859	High Similarity	NPC321958
0.859	High Similarity	NPC321696
0.8588	High Similarity	NPC29587
0.8581	High Similarity	NPC239254
0.8581	High Similarity	NPC172171
0.8571	High Similarity	NPC234730
0.8562	High Similarity	NPC56091
0.8562	High Similarity	NPC245615
0.8562	High Similarity	NPC61604
0.8562	High Similarity	NPC299706
0.8562	High Similarity	NPC115466
0.8553	High Similarity	NPC196420
0.8544	High Similarity	NPC85141
0.8544	High Similarity	NPC240521
0.8537	High Similarity	NPC319749
0.8537	High Similarity	NPC209411
0.8537	High Similarity	NPC15212
0.8537	High Similarity	NPC239890
0.8535	High Similarity	NPC116019
0.8528	High Similarity	NPC215400
0.8528	High Similarity	NPC230531
0.8526	High Similarity	NPC474158
0.8526	High Similarity	NPC180953
0.8526	High Similarity	NPC318286
0.8526	High Similarity	NPC327651
0.8519	High Similarity	NPC29727
0.8519	High Similarity	NPC473323
0.8516	High Similarity	NPC470811
0.8516	High Similarity	NPC255566
0.8516	High Similarity	NPC477696
0.8516	High Similarity	NPC474808
0.8516	High Similarity	NPC12728
0.8516	High Similarity	NPC477697
0.8516	High Similarity	NPC218510
0.8516	High Similarity	NPC76415
0.8516	High Similarity	NPC324962
0.8516	High Similarity	NPC273657
0.8516	High Similarity	NPC106920
0.8516	High Similarity	NPC298317
0.8516	High Similarity	NPC185071
0.8516	High Similarity	NPC265154
0.8512	High Similarity	NPC477883
0.8506	High Similarity	NPC312199
0.8503	High Similarity	NPC215802
0.8503	High Similarity	NPC167231
0.8497	Intermediate Similarity	NPC167045
0.8497	Intermediate Similarity	NPC114120
0.8491	Intermediate Similarity	NPC225815
0.8491	Intermediate Similarity	NPC218041
0.8491	Intermediate Similarity	NPC9933
0.8491	Intermediate Similarity	NPC260781
0.8491	Intermediate Similarity	NPC469707
0.8491	Intermediate Similarity	NPC145979
0.8491	Intermediate Similarity	NPC185955
0.8491	Intermediate Similarity	NPC214326
0.8491	Intermediate Similarity	NPC469706
0.8491	Intermediate Similarity	NPC182368

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 NPC288149 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	286
0.1-0.2	837
0.2-0.3	1666
0.3-0.4	2574
0.4-0.5	2068
0.5-0.6	1049
0.6-0.7	540
0.7-0.8	116
0.8-0.85	5
0.85-0.9	4
0.9-0.95	2
0.95-1	3

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9737	High Similarity	NPD4966	Approved
0.9737	High Similarity	NPD4967	Phase 2
0.9737	High Similarity	NPD4965	Approved
0.9539	High Similarity	NPD37	Approved
0.9484	High Similarity	NPD6234	Discontinued
0.9193	High Similarity	NPD7228	Approved
0.8882	High Similarity	NPD7199	Phase 2
0.8855	High Similarity	NPD7240	Approved
0.8659	High Similarity	NPD7184	Clinical (unspecified phase)
0.8343	Intermediate Similarity	NPD7680	Approved
0.8266	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.8222	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.8176	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.8155	Intermediate Similarity	NPD6232	Discontinued
0.8129	Intermediate Similarity	NPD5844	Phase 1
0.8118	Intermediate Similarity	NPD7473	Discontinued
0.8114	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.807	Intermediate Similarity	NPD3818	Discontinued
0.8025	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7857	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7784	Intermediate Similarity	NPD6559	Discontinued
0.7771	Intermediate Similarity	NPD7074	Phase 3
0.774	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7733	Intermediate Similarity	NPD7229	Phase 3
0.7714	Intermediate Similarity	NPD7054	Approved
0.7702	Intermediate Similarity	NPD6674	Discontinued
0.7677	Intermediate Similarity	NPD3027	Phase 3
0.7674	Intermediate Similarity	NPD8127	Discontinued
0.767	Intermediate Similarity	NPD7472	Approved
0.7651	Intermediate Similarity	NPD1653	Approved
0.7633	Intermediate Similarity	NPD8455	Phase 2
0.7616	Intermediate Similarity	NPD5494	Approved
0.7588	Intermediate Similarity	NPD3817	Phase 2
0.7582	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7576	Intermediate Similarity	NPD2533	Approved
0.7576	Intermediate Similarity	NPD2534	Approved
0.7576	Intermediate Similarity	NPD2532	Approved
0.7576	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7574	Intermediate Similarity	NPD1934	Approved
0.7543	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7543	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7543	Intermediate Similarity	NPD6166	Phase 2
0.7542	Intermediate Similarity	NPD7808	Phase 3
0.7532	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7532	Intermediate Similarity	NPD1613	Approved
0.7529	Intermediate Similarity	NPD3787	Discontinued
0.7529	Intermediate Similarity	NPD1465	Phase 2
0.7529	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7529	Intermediate Similarity	NPD7819	Suspended
0.7528	Intermediate Similarity	NPD6797	Phase 2
0.7516	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD8312	Approved
0.75	Intermediate Similarity	NPD3705	Approved
0.75	Intermediate Similarity	NPD7879	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD8313	Approved
0.75	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.7486	Intermediate Similarity	NPD7251	Discontinued
0.7486	Intermediate Similarity	NPD7685	Pre-registration
0.7456	Intermediate Similarity	NPD7028	Phase 2
0.7442	Intermediate Similarity	NPD3882	Suspended
0.7439	Intermediate Similarity	NPD4110	Phase 3
0.7439	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.743	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7427	Intermediate Similarity	NPD2801	Approved
0.7412	Intermediate Similarity	NPD7615	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD2438	Suspended
0.7394	Intermediate Similarity	NPD6190	Approved
0.7375	Intermediate Similarity	NPD6355	Discontinued
0.7362	Intermediate Similarity	NPD7266	Discontinued
0.7362	Intermediate Similarity	NPD6003	Clinical (unspecified phase)
0.7362	Intermediate Similarity	NPD6006	Clinical (unspecified phase)
0.7362	Intermediate Similarity	NPD6002	Phase 3
0.7362	Intermediate Similarity	NPD6005	Phase 3
0.7362	Intermediate Similarity	NPD6004	Phase 3
0.736	Intermediate Similarity	NPD3751	Discontinued
0.7353	Intermediate Similarity	NPD4380	Phase 2
0.7347	Intermediate Similarity	NPD7827	Phase 1
0.7333	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.7333	Intermediate Similarity	NPD3750	Approved
0.733	Intermediate Similarity	NPD5005	Approved
0.733	Intermediate Similarity	NPD5006	Approved
0.7318	Intermediate Similarity	NPD7804	Clinical (unspecified phase)
0.7317	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7312	Intermediate Similarity	NPD4060	Phase 1
0.7299	Intermediate Similarity	NPD7075	Discontinued
0.7296	Intermediate Similarity	NPD6798	Discontinued
0.7296	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7294	Intermediate Similarity	NPD5808	Clinical (unspecified phase)
0.7294	Intermediate Similarity	NPD7458	Discontinued
0.7284	Intermediate Similarity	NPD7097	Phase 1
0.7283	Intermediate Similarity	NPD5402	Approved
0.7278	Intermediate Similarity	NPD4908	Phase 1
0.7278	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD6959	Discontinued
0.7267	Intermediate Similarity	NPD6801	Discontinued
0.7256	Intermediate Similarity	NPD5763	Approved
0.7256	Intermediate Similarity	NPD5762	Approved
0.7244	Intermediate Similarity	NPD1283	Approved
0.7229	Intermediate Similarity	NPD4628	Phase 3
0.7225	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7219	Intermediate Similarity	NPD7296	Approved
0.7219	Intermediate Similarity	NPD6273	Approved
0.7215	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7211	Intermediate Similarity	NPD4420	Approved
0.7209	Intermediate Similarity	NPD7411	Suspended
0.7205	Intermediate Similarity	NPD2979	Phase 3
0.7205	Intermediate Similarity	NPD3620	Phase 2
0.7205	Intermediate Similarity	NPD4140	Approved
0.7205	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.7195	Intermediate Similarity	NPD6100	Approved
0.7195	Intermediate Similarity	NPD6099	Approved
0.7194	Intermediate Similarity	NPD8151	Discontinued
0.7193	Intermediate Similarity	NPD3226	Approved
0.7184	Intermediate Similarity	NPD8443	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD6233	Phase 2
0.7143	Intermediate Similarity	NPD6663	Approved
0.7143	Intermediate Similarity	NPD7768	Phase 2
0.7134	Intermediate Similarity	NPD3748	Approved
0.7134	Intermediate Similarity	NPD7033	Discontinued
0.7126	Intermediate Similarity	NPD1878	Clinical (unspecified phase)
0.7125	Intermediate Similarity	NPD4625	Phase 3
0.7119	Intermediate Similarity	NPD6746	Phase 2
0.7113	Intermediate Similarity	NPD7435	Discontinued
0.7107	Intermediate Similarity	NPD3018	Phase 2
0.7102	Intermediate Similarity	NPD7975	Clinical (unspecified phase)
0.7102	Intermediate Similarity	NPD3749	Approved
0.7101	Intermediate Similarity	NPD1511	Approved
0.7097	Intermediate Similarity	NPD8434	Phase 2
0.7091	Intermediate Similarity	NPD2935	Discontinued
0.7089	Intermediate Similarity	NPD2797	Approved
0.7083	Intermediate Similarity	NPD5084	Clinical (unspecified phase)
0.7081	Intermediate Similarity	NPD1699	Clinical (unspecified phase)
0.7081	Intermediate Similarity	NPD3764	Approved
0.7078	Intermediate Similarity	NPD1357	Approved
0.7076	Intermediate Similarity	NPD5403	Approved
0.7066	Intermediate Similarity	NPD5698	Clinical (unspecified phase)
0.7066	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7062	Intermediate Similarity	NPD919	Approved
0.7059	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7055	Intermediate Similarity	NPD5124	Phase 1
0.7055	Intermediate Similarity	NPD230	Phase 1
0.7055	Intermediate Similarity	NPD5123	Clinical (unspecified phase)
0.7052	Intermediate Similarity	NPD6599	Discontinued
0.7051	Intermediate Similarity	NPD1281	Approved
0.7051	Intermediate Similarity	NPD1610	Phase 2
0.7047	Intermediate Similarity	NPD6782	Approved
0.7047	Intermediate Similarity	NPD6776	Approved
0.7047	Intermediate Similarity	NPD6780	Approved
0.7047	Intermediate Similarity	NPD6778	Approved
0.7047	Intermediate Similarity	NPD6781	Approved
0.7047	Intermediate Similarity	NPD6779	Approved
0.7047	Intermediate Similarity	NPD6777	Approved
0.7044	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7039	Intermediate Similarity	NPD5710	Approved
0.7039	Intermediate Similarity	NPD5711	Approved
0.7037	Intermediate Similarity	NPD8032	Phase 2
0.7024	Intermediate Similarity	NPD8166	Discontinued
0.7024	Intermediate Similarity	NPD7003	Approved
0.7018	Intermediate Similarity	NPD1512	Approved
0.7018	Intermediate Similarity	NPD1940	Clinical (unspecified phase)
0.7006	Intermediate Similarity	NPD1608	Approved
0.7	Intermediate Similarity	NPD5242	Approved
0.7	Intermediate Similarity	NPD5736	Approved
0.7	Intermediate Similarity	NPD2861	Phase 2
0.7	Intermediate Similarity	NPD6799	Approved
0.7	Intermediate Similarity	NPD3926	Phase 2
0.6975	Remote Similarity	NPD6410	Clinical (unspecified phase)
0.6975	Remote Similarity	NPD3268	Approved
0.6974	Remote Similarity	NPD6823	Phase 2
0.6973	Remote Similarity	NPD7549	Discontinued
0.6962	Remote Similarity	NPD2982	Phase 2
0.6962	Remote Similarity	NPD2983	Phase 2
0.6961	Remote Similarity	NPD7852	Clinical (unspecified phase)
0.6959	Remote Similarity	NPD5401	Approved
0.6951	Remote Similarity	NPD1933	Approved
0.6951	Remote Similarity	NPD447	Suspended
0.6951	Remote Similarity	NPD5735	Approved
0.695	Remote Similarity	NPD7783	Phase 2
0.695	Remote Similarity	NPD7782	Clinical (unspecified phase)
0.6946	Remote Similarity	NPD1550	Clinical (unspecified phase)
0.6946	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.6946	Remote Similarity	NPD2346	Discontinued
0.6943	Remote Similarity	NPD1091	Approved
0.6939	Remote Similarity	NPD7697	Approved
0.6939	Remote Similarity	NPD7696	Phase 3
0.6939	Remote Similarity	NPD7698	Approved
0.6928	Remote Similarity	NPD1510	Phase 2
0.6923	Remote Similarity	NPD4626	Approved
0.6923	Remote Similarity	NPD5125	Phase 3
0.6923	Remote Similarity	NPD5126	Approved
0.6915	Remote Similarity	NPD8150	Discontinued
0.6914	Remote Similarity	NPD7095	Approved
0.6914	Remote Similarity	NPD5952	Clinical (unspecified phase)
0.6909	Remote Similarity	NPD6653	Approved
0.6908	Remote Similarity	NPD5283	Phase 1
0.6905	Remote Similarity	NPD1549	Phase 2
0.6904	Remote Similarity	NPD7870	Phase 2
0.6904	Remote Similarity	NPD7871	Phase 2
0.6901	Remote Similarity	NPD4357	Discontinued
0.69	Remote Similarity	NPD7874	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