NPASS Compound

Structure

NPC470637 OpenBabel07101718322D 30 35 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 2.9345 -1.0827 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 2.0685 -1.5827 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2024 -1.0827 0.0000 C 0 0 2 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 2.0685 -2.5827 0.0000 C 0 0 0 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 2.9345 -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 3.8005 -0.5827 0.0000 N 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 25 1 0 0 0 0 2 3 2 0 0 0 0 2 10 1 0 0 0 0 3 14 1 0 0 0 0 4 10 2 0 0 0 0 4 15 1 0 0 0 0 5 11 2 0 0 0 0 5 16 1 0 0 0 0 6 23 3 0 0 0 0 7 26 1 0 0 0 0 8 27 1 0 0 0 0 8 28 1 0 0 0 0 9 29 1 0 0 0 0 9 30 1 0 0 0 0 11 17 1 0 0 0 0 11 18 1 0 0 0 0 12 6 1 6 0 0 0 12 13 1 0 0 0 0 12 18 1 0 0 0 0 13 7 1 6 0 0 0 13 19 1 0 0 0 0 14 15 2 0 0 0 0 14 27 1 0 0 0 0 15 28 1 0 0 0 0 16 20 2 0 0 0 0 16 29 1 0 0 0 0 17 10 1 1 0 0 0 17 19 1 0 0 0 0 18 21 2 0 0 0 0 19 22 1 1 0 0 0 20 21 1 0 0 0 0 20 30 1 0 0 0 0 21 25 1 0 0 0 0 22 24 2 0 0 0 0 22 26 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	407.1
Volume:	386.53
LogP:	2.547
LogD:	2.386
LogS:	-4.502
# Rotatable Bonds:	2
TPSA:	96.24
# H-Bond Aceptor:	8
# H-Bond Donor:	0
# Rings:	6
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.701
Synthetic Accessibility Score:	4.082
Fsp3:	0.364
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.837
MDCK Permeability:	3.184195884387009e-05
Pgp-inhibitor:	0.493
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.001
20% Bioavailability (F20%):	0.074
30% Bioavailability (F30%):	0.041

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.043
Plasma Protein Binding (PPB):	95.1989517211914%
Volume Distribution (VD):	1.607
Pgp-substrate:	2.3742563724517822%

ADMET: Metabolism

CYP1A2-inhibitor:	0.211
CYP1A2-substrate:	0.93
CYP2C19-inhibitor:	0.941
CYP2C19-substrate:	0.819
CYP2C9-inhibitor:	0.863
CYP2C9-substrate:	0.795
CYP2D6-inhibitor:	0.617
CYP2D6-substrate:	0.121
CYP3A4-inhibitor:	0.951
CYP3A4-substrate:	0.856

ADMET: Excretion

Clearance (CL):	11.383
Half-life (T1/2):	0.111

ADMET: Toxicity

hERG Blockers:	0.049
Human Hepatotoxicity (H-HT):	0.09
Drug-inuced Liver Injury (DILI):	0.897
AMES Toxicity:	0.35
Rat Oral Acute Toxicity:	0.416
Maximum Recommended Daily Dose:	0.983
Skin Sensitization:	0.089
Carcinogencity:	0.173
Eye Corrosion:	0.003
Eye Irritation:	0.124
Respiratory Toxicity:	0.968

Download Data

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

Natural Product: NPC470637

Natural Product ID:	NPC470637
*Common Name:**	(5S,5Ar,8Ar,9R)-9-(1,3-Benzodioxol-5-Yl)-4-Methoxy-8-Oxo-5A,6,8A,9-Tetrahydro-5H-[2]Benzofuro[6,5-F][1,3]Benzodioxole-5-Carbonitrile
IUPAC Name:	(5S,5aR,8aR,9R)-9-(1,3-benzodioxol-5-yl)-4-methoxy-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxole-5-carbonitrile
Synonyms:
Standard InCHIKey:	BLNRXJFJIJOONY-TZOHYUNLSA-N
Standard InCHI:	InChI=1S/C22H17NO7/c1-25-21-18-11(5-16-20(21)30-9-29-16)17(10-2-3-14-15(4-10)28-8-27-14)19-13(12(18)6-23)7-26-22(19)24/h2-5,12-13,17,19H,7-9H2,1H3/t12-,13+,17+,19-/m0/s1
SMILES:	COC1=C2C(C3COC(=O)C3C(C2=CC4=C1OCO4)C5=CC6=C(C=C5)OCO6)C#N
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2146938
PubChem CID:	71451057
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	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	IC50	=	1.2	ug.mL-1	PMID[506164]

☑ 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 NPC470637 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	331
0.1-0.2	1527
0.2-0.3	3295
0.3-0.4	9250
0.4-0.5	10085
0.5-0.6	4811
0.6-0.7	10936
0.7-0.8	2262
0.8-0.85	140
0.85-0.9	42
0.9-0.95	16
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9338	High Similarity	NPC177476
0.9338	High Similarity	NPC262455
0.9276	High Similarity	NPC149505
0.9205	High Similarity	NPC104024
0.9205	High Similarity	NPC65574
0.9205	High Similarity	NPC80230
0.9205	High Similarity	NPC101755
0.9205	High Similarity	NPC304687
0.9114	High Similarity	NPC96593
0.9091	High Similarity	NPC210642
0.9091	High Similarity	NPC13985
0.9057	High Similarity	NPC288149
0.9038	High Similarity	NPC273578
0.9007	High Similarity	NPC177644
0.9007	High Similarity	NPC191158
0.8882	High Similarity	NPC218841
0.8882	High Similarity	NPC92693
0.8874	High Similarity	NPC176586
0.8874	High Similarity	NPC210354
0.8868	High Similarity	NPC163527
0.8868	High Similarity	NPC181168
0.8868	High Similarity	NPC207584
0.8868	High Similarity	NPC115281
0.8868	High Similarity	NPC19947
0.8808	High Similarity	NPC162851
0.8808	High Similarity	NPC218092
0.8808	High Similarity	NPC246474
0.8805	High Similarity	NPC237946
0.8805	High Similarity	NPC32373
0.8797	High Similarity	NPC30009
0.8797	High Similarity	NPC103197
0.8774	High Similarity	NPC262804
0.8774	High Similarity	NPC40654
0.8766	High Similarity	NPC193779
0.875	High Similarity	NPC151423
0.875	High Similarity	NPC40237
0.8726	High Similarity	NPC303519
0.8696	High Similarity	NPC474043
0.8688	High Similarity	NPC473900
0.8642	High Similarity	NPC150943
0.8642	High Similarity	NPC91634
0.8642	High Similarity	NPC119910
0.8642	High Similarity	NPC268718
0.8636	High Similarity	NPC475000
0.8634	High Similarity	NPC19600
0.8625	High Similarity	NPC234730
0.8616	High Similarity	NPC245948
0.8589	High Similarity	NPC152424
0.8589	High Similarity	NPC100465
0.8571	High Similarity	NPC115123
0.8571	High Similarity	NPC474288
0.8571	High Similarity	NPC239113
0.8562	High Similarity	NPC348849
0.8562	High Similarity	NPC178195
0.8545	High Similarity	NPC222531
0.8497	Intermediate Similarity	NPC470642
0.8491	Intermediate Similarity	NPC164082
0.8487	Intermediate Similarity	NPC196420
0.8485	Intermediate Similarity	NPC14294
0.8485	Intermediate Similarity	NPC116759
0.8481	Intermediate Similarity	NPC216223
0.8481	Intermediate Similarity	NPC145569
0.8477	Intermediate Similarity	NPC211386
0.8476	Intermediate Similarity	NPC209411
0.8476	Intermediate Similarity	NPC115624
0.8476	Intermediate Similarity	NPC239890
0.8476	Intermediate Similarity	NPC191352
0.8476	Intermediate Similarity	NPC258322
0.8476	Intermediate Similarity	NPC15212
0.8447	Intermediate Similarity	NPC54179
0.8415	Intermediate Similarity	NPC78944
0.8411	Intermediate Similarity	NPC19890
0.8411	Intermediate Similarity	NPC110958
0.8397	Intermediate Similarity	NPC18211
0.8383	Intermediate Similarity	NPC174734
0.8383	Intermediate Similarity	NPC306475
0.8383	Intermediate Similarity	NPC474042
0.8375	Intermediate Similarity	NPC474975
0.8365	Intermediate Similarity	NPC293757
0.8365	Intermediate Similarity	NPC668
0.8365	Intermediate Similarity	NPC174512
0.8365	Intermediate Similarity	NPC477698
0.8365	Intermediate Similarity	NPC474965
0.8365	Intermediate Similarity	NPC477695
0.8355	Intermediate Similarity	NPC72796
0.8355	Intermediate Similarity	NPC44245
0.8354	Intermediate Similarity	NPC125713
0.8344	Intermediate Similarity	NPC205915
0.8344	Intermediate Similarity	NPC474158
0.8333	Intermediate Similarity	NPC185498
0.8323	Intermediate Similarity	NPC56184
0.8313	Intermediate Similarity	NPC22130
0.8313	Intermediate Similarity	NPC198796
0.8313	Intermediate Similarity	NPC24425
0.8313	Intermediate Similarity	NPC116838
0.8305	Intermediate Similarity	NPC470646
0.8301	Intermediate Similarity	NPC11453
0.8291	Intermediate Similarity	NPC321696
0.8291	Intermediate Similarity	NPC321958
0.8291	Intermediate Similarity	NPC87295
0.8291	Intermediate Similarity	NPC3982
0.8284	Intermediate Similarity	NPC117911
0.8282	Intermediate Similarity	NPC188962
0.8282	Intermediate Similarity	NPC202249
0.8282	Intermediate Similarity	NPC42871
0.828	Intermediate Similarity	NPC143092
0.828	Intermediate Similarity	NPC474036
0.8272	Intermediate Similarity	NPC178574
0.8272	Intermediate Similarity	NPC65591
0.8269	Intermediate Similarity	NPC474295
0.8261	Intermediate Similarity	NPC477700
0.8253	Intermediate Similarity	NPC319749
0.825	Intermediate Similarity	NPC85141
0.8235	Intermediate Similarity	NPC474139
0.8235	Intermediate Similarity	NPC189474
0.8235	Intermediate Similarity	NPC179240
0.8232	Intermediate Similarity	NPC301897
0.8228	Intermediate Similarity	NPC318286
0.8228	Intermediate Similarity	NPC327651
0.8225	Intermediate Similarity	NPC79322
0.8217	Intermediate Similarity	NPC218510
0.8217	Intermediate Similarity	NPC76415
0.8212	Intermediate Similarity	NPC192255
0.821	Intermediate Similarity	NPC104353
0.821	Intermediate Similarity	NPC477699
0.8205	Intermediate Similarity	NPC312199
0.8204	Intermediate Similarity	NPC280778
0.8204	Intermediate Similarity	NPC61141
0.8187	Intermediate Similarity	NPC304821
0.8187	Intermediate Similarity	NPC181464
0.8182	Intermediate Similarity	NPC143895
0.8182	Intermediate Similarity	NPC102260
0.8182	Intermediate Similarity	NPC230968
0.8176	Intermediate Similarity	NPC33832
0.817	Intermediate Similarity	NPC31530
0.8166	Intermediate Similarity	NPC471923
0.8165	Intermediate Similarity	NPC477701
0.8165	Intermediate Similarity	NPC326144
0.8165	Intermediate Similarity	NPC166884
0.8165	Intermediate Similarity	NPC141569
0.816	Intermediate Similarity	NPC477377
0.816	Intermediate Similarity	NPC474514
0.815	Intermediate Similarity	NPC196771
0.8148	Intermediate Similarity	NPC32079
0.8141	Intermediate Similarity	NPC216434
0.8141	Intermediate Similarity	NPC103448
0.814	Intermediate Similarity	NPC184624
0.8137	Intermediate Similarity	NPC127827
0.8137	Intermediate Similarity	NPC24193
0.8133	Intermediate Similarity	NPC325122
0.8129	Intermediate Similarity	NPC14022
0.8121	Intermediate Similarity	NPC477380
0.8118	Intermediate Similarity	NPC475453
0.8118	Intermediate Similarity	NPC473531
0.8117	Intermediate Similarity	NPC49235
0.8117	Intermediate Similarity	NPC148893
0.8117	Intermediate Similarity	NPC25333
0.8113	Intermediate Similarity	NPC205316
0.811	Intermediate Similarity	NPC136757
0.8107	Intermediate Similarity	NPC477884
0.8105	Intermediate Similarity	NPC266848
0.8105	Intermediate Similarity	NPC136750
0.8101	Intermediate Similarity	NPC273657
0.8101	Intermediate Similarity	NPC106920
0.8098	Intermediate Similarity	NPC477378
0.8098	Intermediate Similarity	NPC475229
0.8086	Intermediate Similarity	NPC475722
0.8086	Intermediate Similarity	NPC316989
0.8086	Intermediate Similarity	NPC473989
0.8084	Intermediate Similarity	NPC474770
0.8075	Intermediate Similarity	NPC477375
0.8075	Intermediate Similarity	NPC327352
0.8075	Intermediate Similarity	NPC252281
0.8075	Intermediate Similarity	NPC198129
0.8072	Intermediate Similarity	NPC477885
0.8065	Intermediate Similarity	NPC209229
0.8065	Intermediate Similarity	NPC32189
0.8061	Intermediate Similarity	NPC238834
0.8061	Intermediate Similarity	NPC186316
0.8059	Intermediate Similarity	NPC118162
0.8059	Intermediate Similarity	NPC83049
0.8059	Intermediate Similarity	NPC320471
0.8049	Intermediate Similarity	NPC144162
0.8039	Intermediate Similarity	NPC72046
0.8039	Intermediate Similarity	NPC7744
0.8039	Intermediate Similarity	NPC65183
0.8039	Intermediate Similarity	NPC261812
0.8038	Intermediate Similarity	NPC472562
0.8038	Intermediate Similarity	NPC80326
0.8038	Intermediate Similarity	NPC287124
0.8038	Intermediate Similarity	NPC191231
0.8035	Intermediate Similarity	NPC474568
0.8025	Intermediate Similarity	NPC322426
0.8025	Intermediate Similarity	NPC477376
0.8025	Intermediate Similarity	NPC477374
0.8012	Intermediate Similarity	NPC311912
0.8012	Intermediate Similarity	NPC116019
0.8	Intermediate Similarity	NPC35266
0.8	Intermediate Similarity	NPC312763
0.8	Intermediate Similarity	NPC198461

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 NPC470637 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	262
0.1-0.2	862
0.2-0.3	1553
0.3-0.4	2746
0.4-0.5	2026
0.5-0.6	1115
0.6-0.7	536
0.7-0.8	42
0.8-0.85	4
0.85-0.9	4
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8805	High Similarity	NPD4966	Approved
0.8805	High Similarity	NPD4967	Phase 2
0.8805	High Similarity	NPD4965	Approved
0.8696	High Similarity	NPD6234	Discontinued
0.8616	High Similarity	NPD37	Approved
0.8364	Intermediate Similarity	NPD7199	Phase 2
0.8333	Intermediate Similarity	NPD7228	Approved
0.8263	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.8208	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.814	Intermediate Similarity	NPD7240	Approved
0.7963	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7812	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7812	Intermediate Similarity	NPD4110	Phase 3
0.7778	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7772	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.7606	Intermediate Similarity	NPD7680	Approved
0.7572	Intermediate Similarity	NPD6232	Discontinued
0.7543	Intermediate Similarity	NPD7473	Discontinued
0.746	Intermediate Similarity	NPD5005	Approved
0.746	Intermediate Similarity	NPD5006	Approved
0.7459	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7458	Intermediate Similarity	NPD5844	Phase 1
0.7457	Intermediate Similarity	NPD5494	Approved
0.7439	Intermediate Similarity	NPD5084	Clinical (unspecified phase)
0.7434	Intermediate Similarity	NPD3705	Approved
0.7371	Intermediate Similarity	NPD7229	Phase 3
0.7346	Intermediate Similarity	NPD2438	Suspended
0.734	Intermediate Similarity	NPD4420	Approved
0.7303	Intermediate Similarity	NPD3818	Discontinued
0.725	Intermediate Similarity	NPD2979	Phase 3
0.7233	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7232	Intermediate Similarity	NPD5242	Approved
0.7225	Intermediate Similarity	NPD3817	Phase 2
0.7208	Intermediate Similarity	NPD7827	Phase 1
0.7193	Intermediate Similarity	NPD7028	Phase 2
0.7186	Intermediate Similarity	NPD7124	Phase 2
0.7184	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7178	Intermediate Similarity	NPD3748	Approved
0.7168	Intermediate Similarity	NPD7819	Suspended
0.7151	Intermediate Similarity	NPD6873	Phase 2
0.7151	Intermediate Similarity	NPD7615	Clinical (unspecified phase)
0.7119	Intermediate Similarity	NPD8127	Discontinued
0.7108	Intermediate Similarity	NPD6674	Discontinued
0.7102	Intermediate Similarity	NPD919	Approved
0.7101	Intermediate Similarity	NPD2533	Approved
0.7101	Intermediate Similarity	NPD2532	Approved
0.7101	Intermediate Similarity	NPD2534	Approved
0.7097	Intermediate Similarity	NPD1281	Approved
0.7086	Intermediate Similarity	NPD3882	Suspended
0.7081	Intermediate Similarity	NPD8032	Phase 2
0.7049	Intermediate Similarity	NPD6559	Discontinued
0.7033	Intermediate Similarity	NPD7074	Phase 3
0.7032	Intermediate Similarity	NPD3847	Discontinued
0.7029	Intermediate Similarity	NPD5353	Approved
0.7012	Intermediate Similarity	NPD6111	Discontinued
0.7011	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7011	Intermediate Similarity	NPD1934	Approved
0.7	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD4481	Phase 3
0.6994	Remote Similarity	NPD4972	Discontinued
0.6994	Remote Similarity	NPD6355	Discontinued
0.6994	Remote Similarity	NPD1933	Approved
0.6984	Remote Similarity	NPD7296	Approved
0.6983	Remote Similarity	NPD3787	Discontinued
0.6978	Remote Similarity	NPD7054	Approved
0.6971	Remote Similarity	NPD2801	Approved
0.6971	Remote Similarity	NPD2393	Clinical (unspecified phase)
0.6971	Remote Similarity	NPD8455	Phase 2
0.6971	Remote Similarity	NPD1465	Phase 2
0.6968	Remote Similarity	NPD8397	Clinical (unspecified phase)
0.6966	Remote Similarity	NPD6746	Phase 2
0.6964	Remote Similarity	NPD6398	Clinical (unspecified phase)
0.6964	Remote Similarity	NPD3750	Approved
0.6962	Remote Similarity	NPD1283	Approved
0.6959	Remote Similarity	NPD1940	Clinical (unspecified phase)
0.6957	Remote Similarity	NPD3027	Phase 3
0.6954	Remote Similarity	NPD6386	Approved
0.6954	Remote Similarity	NPD6385	Approved
0.6954	Remote Similarity	NPD5283	Phase 1
0.6946	Remote Similarity	NPD970	Clinical (unspecified phase)
0.6944	Remote Similarity	NPD3926	Phase 2
0.694	Remote Similarity	NPD7472	Approved
0.6937	Remote Similarity	NPD3018	Phase 2
0.6936	Remote Similarity	NPD7458	Discontinued
0.6933	Remote Similarity	NPD4060	Phase 1
0.6928	Remote Similarity	NPD4476	Approved
0.6928	Remote Similarity	NPD2531	Phase 2
0.6928	Remote Similarity	NPD4477	Approved
0.6923	Remote Similarity	NPD5307	Clinical (unspecified phase)
0.6914	Remote Similarity	NPD6798	Discontinued
0.6914	Remote Similarity	NPD4907	Clinical (unspecified phase)
0.6903	Remote Similarity	NPD1651	Approved
0.6903	Remote Similarity	NPD5691	Approved
0.6897	Remote Similarity	NPD6599	Discontinued
0.6894	Remote Similarity	NPD4908	Phase 1
0.6889	Remote Similarity	NPD5710	Approved
0.6889	Remote Similarity	NPD5711	Approved
0.6882	Remote Similarity	NPD2971	Approved
0.6882	Remote Similarity	NPD2968	Approved
0.6879	Remote Similarity	NPD1653	Approved
0.6878	Remote Similarity	NPD7235	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD5563	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD7096	Clinical (unspecified phase)
0.6871	Remote Similarity	NPD4870	Approved
0.6867	Remote Similarity	NPD4108	Discontinued
0.6859	Remote Similarity	NPD17	Approved
0.6845	Remote Similarity	NPD2897	Discontinued
0.6845	Remote Similarity	NPD2424	Discontinued
0.6842	Remote Similarity	NPD6799	Approved
0.6842	Remote Similarity	NPD4357	Discontinued
0.6835	Remote Similarity	NPD2981	Phase 2
0.6833	Remote Similarity	NPD1247	Approved
0.6829	Remote Similarity	NPD1612	Clinical (unspecified phase)
0.6829	Remote Similarity	NPD1613	Approved
0.6828	Remote Similarity	NPD7808	Phase 3
0.6828	Remote Similarity	NPD7549	Discontinued
0.6826	Remote Similarity	NPD6100	Approved
0.6826	Remote Similarity	NPD2796	Approved
0.6826	Remote Similarity	NPD6099	Approved
0.6813	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.6813	Remote Similarity	NPD6166	Phase 2
0.6813	Remote Similarity	NPD6168	Clinical (unspecified phase)
0.6811	Remote Similarity	NPD6797	Phase 2
0.6806	Remote Similarity	NPD7879	Clinical (unspecified phase)
0.6802	Remote Similarity	NPD7446	Clinical (unspecified phase)
0.6802	Remote Similarity	NPD3688	Clinical (unspecified phase)
0.6802	Remote Similarity	NPD3146	Approved
0.68	Remote Similarity	NPD8151	Discontinued
0.6798	Remote Similarity	NPD7768	Phase 2
0.6792	Remote Similarity	NPD2982	Phase 2
0.6792	Remote Similarity	NPD2983	Phase 2
0.6791	Remote Similarity	NPD8313	Approved
0.6791	Remote Similarity	NPD8312	Approved
0.679	Remote Similarity	NPD1529	Clinical (unspecified phase)
0.6788	Remote Similarity	NPD3657	Discovery
0.6788	Remote Similarity	NPD4618	Approved
0.6788	Remote Similarity	NPD4622	Approved
0.6786	Remote Similarity	NPD5763	Approved
0.6786	Remote Similarity	NPD5762	Approved
0.6774	Remote Similarity	NPD7251	Discontinued
0.6774	Remote Similarity	NPD7685	Pre-registration
0.6765	Remote Similarity	NPD7466	Approved
0.6763	Remote Similarity	NPD7314	Clinical (unspecified phase)
0.6763	Remote Similarity	NPD6273	Approved
0.6761	Remote Similarity	NPD7411	Suspended
0.676	Remote Similarity	NPD7075	Discontinued
0.676	Remote Similarity	NPD6971	Discontinued
0.676	Remote Similarity	NPD3749	Approved
0.676	Remote Similarity	NPD7975	Clinical (unspecified phase)
0.676	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.6753	Remote Similarity	NPD2974	Approved
0.6753	Remote Similarity	NPD2975	Approved
0.6753	Remote Similarity	NPD2973	Approved
0.6748	Remote Similarity	NPD4625	Phase 3
0.6747	Remote Similarity	NPD4579	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD7837	Clinical (unspecified phase)
0.6743	Remote Similarity	NPD4005	Discontinued
0.6743	Remote Similarity	NPD5808	Clinical (unspecified phase)
0.6739	Remote Similarity	NPD3751	Discontinued
0.6739	Remote Similarity	NPD6620	Discovery
0.6735	Remote Similarity	NPD4580	Approved
0.673	Remote Similarity	NPD1608	Approved
0.6728	Remote Similarity	NPD1530	Clinical (unspecified phase)
0.6727	Remote Similarity	NPD4140	Approved
0.6724	Remote Similarity	NPD920	Approved
0.6724	Remote Similarity	NPD7427	Discontinued
0.6723	Remote Similarity	NPD3384	Approved
0.6723	Remote Similarity	NPD6801	Discontinued
0.6723	Remote Similarity	NPD3383	Approved
0.6723	Remote Similarity	NPD3382	Approved
0.672	Remote Similarity	NPD7993	Clinical (unspecified phase)
0.6717	Remote Similarity	NPD7435	Discontinued
0.6708	Remote Similarity	NPD3266	Approved
0.6708	Remote Similarity	NPD2797	Approved
0.6708	Remote Similarity	NPD3267	Approved
0.6707	Remote Similarity	NPD5689	Approved
0.6707	Remote Similarity	NPD5109	Approved
0.6707	Remote Similarity	NPD5110	Phase 2
0.6707	Remote Similarity	NPD5111	Phase 2
0.6707	Remote Similarity	NPD6895	Approved
0.6707	Remote Similarity	NPD5688	Approved
0.6707	Remote Similarity	NPD6896	Approved
0.6707	Remote Similarity	NPD1296	Phase 2
0.6707	Remote Similarity	NPD3764	Approved
0.6707	Remote Similarity	NPD7097	Phase 1
0.6706	Remote Similarity	NPD7421	Clinical (unspecified phase)
0.6704	Remote Similarity	NPD5019	Clinical (unspecified phase)
0.6703	Remote Similarity	NPD7315	Approved
0.6702	Remote Similarity	NPD7281	Phase 3
0.6702	Remote Similarity	NPD7280	Phase 3
0.6686	Remote Similarity	NPD6002	Phase 3
0.6686	Remote Similarity	NPD6006	Clinical (unspecified phase)
0.6686	Remote Similarity	NPD6003	Clinical (unspecified phase)
0.6686	Remote Similarity	NPD6783	Clinical (unspecified phase)
0.6686	Remote Similarity	NPD6005	Phase 3
0.6686	Remote Similarity	NPD6004	Phase 3
0.6682	Remote Similarity	NPD6723	Discontinued
0.6667	Remote Similarity	NPD6663	Approved
0.6667	Remote Similarity	NPD1878	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD3647	Clinical (unspecified phase)

Bioactivity similarity: Similar Natural Products in NPASS

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

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

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data