NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	339.15
Volume:	347.953
LogP:	2.683
LogD:	3.285
LogS:	-3.284
# Rotatable Bonds:	3
TPSA:	57.56
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.776
Synthetic Accessibility Score:	4.509
Fsp3:	0.3
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.835
MDCK Permeability:	3.10323121084366e-05
Pgp-inhibitor:	0.006
Pgp-substrate:	0.999
Human Intestinal Absorption (HIA):	0.011
20% Bioavailability (F20%):	0.087
30% Bioavailability (F30%):	0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.721
Plasma Protein Binding (PPB):	92.38591003417969%
Volume Distribution (VD):	1.268
Pgp-substrate:	10.002337455749512%

ADMET: Metabolism

CYP1A2-inhibitor:	0.766
CYP1A2-substrate:	0.677
CYP2C19-inhibitor:	0.278
CYP2C19-substrate:	0.885
CYP2C9-inhibitor:	0.243
CYP2C9-substrate:	0.813
CYP2D6-inhibitor:	0.064
CYP2D6-substrate:	0.519
CYP3A4-inhibitor:	0.396
CYP3A4-substrate:	0.683

ADMET: Excretion

Clearance (CL):	5.643
Half-life (T1/2):	0.86

ADMET: Toxicity

hERG Blockers:	0.434
Human Hepatotoxicity (H-HT):	0.693
Drug-inuced Liver Injury (DILI):	0.362
AMES Toxicity:	0.577
Rat Oral Acute Toxicity:	0.625
Maximum Recommended Daily Dose:	0.984
Skin Sensitization:	0.668
Carcinogencity:	0.17
Eye Corrosion:	0.004
Eye Irritation:	0.047
Respiratory Toxicity:	0.957

Download Data

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

Natural Product: NPC476569

Natural Product ID:	NPC476569
*Common Name:**	(13aS)-2,3,9-trimethoxy-5,6,13,13a-tetrahydroisoquinolino[2,1-b]isoquinolin-7-ium-10-ol;2,2,2-trifluoroacetate
IUPAC Name:	(13aS)-2,3,9-trimethoxy-5,6,13,13a-tetrahydroisoquinolino[2,1-b]isoquinolin-7-ium-10-ol;2,2,2-trifluoroacetate
Synonyms:
Standard InCHIKey:	JXMGCJNBVUYMLA-NTISSMGPSA-N
Standard InCHI:	InChI=1S/C20H21NO4.C2HF3O2/c1-23-18-9-13-6-7-21-11-15-12(4-5-17(22)20(15)25-3)8-16(21)14(13)10-19(18)24-2;3-2(4,5)1(6)7/h4-5,9-11,16H,6-8H2,1-3H3;(H,6,7)/t16-;/m0./s1
SMILES:	COC1=C(C=C2[C@@H]3CC4=C(C=[N+]3CCC2=C1)C(=C(C=C4)O)OC)OC.C(=O)(C(F)(F)F)[O-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	49831396
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002955] Tetrahydroisoquinolines

*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
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	n.a.	stem wood	n.a.	DOI[10.1021/np100247r]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10395501]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10425140]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[15568797]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	stem	Taipei Botanical Garden, Taipei, Taiwan, China	2006-MAR	PMID[20828184]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	fruits	n.a.	n.a.	PMID[25499882]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9584397]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9599260]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6333	Annona glabra	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6333	Annona glabra	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	1

Activity Type	# Activity
Individual Protein	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT66	Individual Protein	Acetylcholinesterase	Electrophorus electricus	IC50	=	30800	nM	PMID[20828184]

☑ 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 NPC476569 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	263
0.1-0.2	1341
0.2-0.3	5365
0.3-0.4	12084
0.4-0.5	5745
0.5-0.6	15399
0.6-0.7	2072
0.7-0.8	422
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9286	High Similarity	NPC57512
0.9091	High Similarity	NPC476580
0.8903	High Similarity	NPC476579
0.882	High Similarity	NPC306669
0.8614	High Similarity	NPC4669
0.8544	High Similarity	NPC85747
0.8544	High Similarity	NPC8337
0.8457	Intermediate Similarity	NPC106786
0.8415	Intermediate Similarity	NPC59567
0.8387	Intermediate Similarity	NPC476567
0.8387	Intermediate Similarity	NPC136860
0.8387	Intermediate Similarity	NPC128019
0.8377	Intermediate Similarity	NPC474915
0.8377	Intermediate Similarity	NPC213206
0.8377	Intermediate Similarity	NPC188163
0.8377	Intermediate Similarity	NPC328750
0.8312	Intermediate Similarity	NPC314682
0.8294	Intermediate Similarity	NPC222524
0.8232	Intermediate Similarity	NPC118804
0.8199	Intermediate Similarity	NPC119669
0.8199	Intermediate Similarity	NPC476568
0.8182	Intermediate Similarity	NPC226428
0.8182	Intermediate Similarity	NPC475780
0.8176	Intermediate Similarity	NPC476144
0.8176	Intermediate Similarity	NPC210437
0.8176	Intermediate Similarity	NPC51957
0.8176	Intermediate Similarity	NPC106295
0.8176	Intermediate Similarity	NPC16107
0.815	Intermediate Similarity	NPC298339
0.8137	Intermediate Similarity	NPC223125
0.8133	Intermediate Similarity	NPC153631
0.8125	Intermediate Similarity	NPC7467
0.8092	Intermediate Similarity	NPC27887
0.8079	Intermediate Similarity	NPC160193
0.805	Intermediate Similarity	NPC185838
0.805	Intermediate Similarity	NPC130926
0.8047	Intermediate Similarity	NPC471604
0.8037	Intermediate Similarity	NPC223124
0.8036	Intermediate Similarity	NPC3375
0.8036	Intermediate Similarity	NPC255607
0.8025	Intermediate Similarity	NPC220858
0.8025	Intermediate Similarity	NPC97221
0.8025	Intermediate Similarity	NPC88249
0.8025	Intermediate Similarity	NPC151895
0.8025	Intermediate Similarity	NPC192768
0.8012	Intermediate Similarity	NPC428
0.8012	Intermediate Similarity	NPC24233
0.8012	Intermediate Similarity	NPC476571
0.8012	Intermediate Similarity	NPC475959
0.8012	Intermediate Similarity	NPC147390
0.8012	Intermediate Similarity	NPC135538
0.8012	Intermediate Similarity	NPC246587
0.8011	Intermediate Similarity	NPC214629
0.7966	Intermediate Similarity	NPC477259
0.7966	Intermediate Similarity	NPC169387
0.795	Intermediate Similarity	NPC191376
0.795	Intermediate Similarity	NPC321505
0.795	Intermediate Similarity	NPC179825
0.7949	Intermediate Similarity	NPC253429
0.7929	Intermediate Similarity	NPC39103
0.7929	Intermediate Similarity	NPC2770
0.7927	Intermediate Similarity	NPC233029
0.7927	Intermediate Similarity	NPC210148
0.7921	Intermediate Similarity	NPC208890
0.7904	Intermediate Similarity	NPC216816
0.7895	Intermediate Similarity	NPC86469
0.7895	Intermediate Similarity	NPC470324
0.7874	Intermediate Similarity	NPC35680
0.7866	Intermediate Similarity	NPC326316
0.7866	Intermediate Similarity	NPC81733
0.7857	Intermediate Similarity	NPC135006
0.7853	Intermediate Similarity	NPC116007
0.784	Intermediate Similarity	NPC476151
0.7836	Intermediate Similarity	NPC284842
0.7833	Intermediate Similarity	NPC63152
0.7831	Intermediate Similarity	NPC172765
0.7831	Intermediate Similarity	NPC278799
0.7831	Intermediate Similarity	NPC138487
0.7831	Intermediate Similarity	NPC189266
0.7831	Intermediate Similarity	NPC276588
0.7831	Intermediate Similarity	NPC54379
0.7831	Intermediate Similarity	NPC204828
0.7831	Intermediate Similarity	NPC2413
0.7831	Intermediate Similarity	NPC184026
0.7831	Intermediate Similarity	NPC249797
0.7831	Intermediate Similarity	NPC39701
0.7831	Intermediate Similarity	NPC207757
0.7831	Intermediate Similarity	NPC193949
0.7831	Intermediate Similarity	NPC5238
0.7831	Intermediate Similarity	NPC127674
0.7831	Intermediate Similarity	NPC80129
0.7831	Intermediate Similarity	NPC216459
0.7831	Intermediate Similarity	NPC99659
0.7831	Intermediate Similarity	NPC187022
0.7831	Intermediate Similarity	NPC325871
0.7831	Intermediate Similarity	NPC295691
0.7831	Intermediate Similarity	NPC469817
0.7831	Intermediate Similarity	NPC41178
0.7831	Intermediate Similarity	NPC93593
0.7831	Intermediate Similarity	NPC110416
0.7824	Intermediate Similarity	NPC231198
0.7818	Intermediate Similarity	NPC37272
0.7805	Intermediate Similarity	NPC274026
0.7803	Intermediate Similarity	NPC303581
0.7803	Intermediate Similarity	NPC67978
0.7791	Intermediate Similarity	NPC130941
0.7784	Intermediate Similarity	NPC25084
0.7784	Intermediate Similarity	NPC146288
0.7784	Intermediate Similarity	NPC247639
0.7746	Intermediate Similarity	NPC474708
0.7744	Intermediate Similarity	NPC103379
0.7744	Intermediate Similarity	NPC92541
0.7744	Intermediate Similarity	NPC207824
0.7744	Intermediate Similarity	NPC219162
0.7744	Intermediate Similarity	NPC477565
0.7744	Intermediate Similarity	NPC60538
0.774	Intermediate Similarity	NPC115906
0.7738	Intermediate Similarity	NPC476572
0.7735	Intermediate Similarity	NPC226708
0.7725	Intermediate Similarity	NPC78733
0.7714	Intermediate Similarity	NPC308267
0.7711	Intermediate Similarity	NPC58661
0.7711	Intermediate Similarity	NPC82285
0.7711	Intermediate Similarity	NPC470924
0.7711	Intermediate Similarity	NPC133011
0.7711	Intermediate Similarity	NPC148898
0.7707	Intermediate Similarity	NPC11147
0.7705	Intermediate Similarity	NPC477258
0.7697	Intermediate Similarity	NPC102760
0.7692	Intermediate Similarity	NPC111485
0.7692	Intermediate Similarity	NPC160692
0.7688	Intermediate Similarity	NPC475845
0.7684	Intermediate Similarity	NPC149285
0.7679	Intermediate Similarity	NPC31311
0.7679	Intermediate Similarity	NPC234392
0.7679	Intermediate Similarity	NPC147091
0.7676	Intermediate Similarity	NPC267414
0.767	Intermediate Similarity	NPC241704
0.7663	Intermediate Similarity	NPC24228
0.7658	Intermediate Similarity	NPC131204
0.7658	Intermediate Similarity	NPC301050
0.7658	Intermediate Similarity	NPC7018
0.7654	Intermediate Similarity	NPC83511
0.7651	Intermediate Similarity	NPC76213
0.7651	Intermediate Similarity	NPC218575
0.7651	Intermediate Similarity	NPC277669
0.7647	Intermediate Similarity	NPC205167
0.763	Intermediate Similarity	NPC474324
0.763	Intermediate Similarity	NPC57812
0.7627	Intermediate Similarity	NPC21885
0.7622	Intermediate Similarity	NPC95075
0.7622	Intermediate Similarity	NPC144863
0.7622	Intermediate Similarity	NPC253883
0.7622	Intermediate Similarity	NPC90844
0.7597	Intermediate Similarity	NPC172403
0.7588	Intermediate Similarity	NPC92191
0.7588	Intermediate Similarity	NPC477080
0.7588	Intermediate Similarity	NPC59028
0.7586	Intermediate Similarity	NPC66573
0.7584	Intermediate Similarity	NPC32154
0.7574	Intermediate Similarity	NPC126519
0.7574	Intermediate Similarity	NPC170503
0.7574	Intermediate Similarity	NPC203784
0.7569	Intermediate Similarity	NPC230098
0.7569	Intermediate Similarity	NPC162694
0.7568	Intermediate Similarity	NPC279665
0.7558	Intermediate Similarity	NPC324144
0.7558	Intermediate Similarity	NPC475393
0.7554	Intermediate Similarity	NPC469816
0.7554	Intermediate Similarity	NPC469815
0.7546	Intermediate Similarity	NPC294249
0.7544	Intermediate Similarity	NPC27410
0.7544	Intermediate Similarity	NPC232924
0.7544	Intermediate Similarity	NPC249274
0.7544	Intermediate Similarity	NPC477559
0.7544	Intermediate Similarity	NPC166014
0.7544	Intermediate Similarity	NPC160298
0.7544	Intermediate Similarity	NPC266753
0.7544	Intermediate Similarity	NPC306902
0.753	Intermediate Similarity	NPC44869
0.7528	Intermediate Similarity	NPC121400
0.7527	Intermediate Similarity	NPC14622
0.7527	Intermediate Similarity	NPC215098
0.7527	Intermediate Similarity	NPC124302
0.7527	Intermediate Similarity	NPC46744
0.7527	Intermediate Similarity	NPC166979
0.7527	Intermediate Similarity	NPC71124
0.7527	Intermediate Similarity	NPC73020
0.7527	Intermediate Similarity	NPC70290
0.7516	Intermediate Similarity	NPC118419
0.7515	Intermediate Similarity	NPC244112
0.7514	Intermediate Similarity	NPC13504
0.7514	Intermediate Similarity	NPC276944
0.7514	Intermediate Similarity	NPC477563
0.7514	Intermediate Similarity	NPC167546
0.7514	Intermediate Similarity	NPC121275
0.7514	Intermediate Similarity	NPC284183
0.7514	Intermediate Similarity	NPC196447
0.7514	Intermediate Similarity	NPC253043
0.7514	Intermediate Similarity	NPC302527

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 NPC476569 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	181
0.1-0.2	660
0.2-0.3	1063
0.3-0.4	2012
0.4-0.5	2726
0.5-0.6	1982
0.6-0.7	462
0.7-0.8	61
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8774	High Similarity	NPD3639	Approved
0.8774	High Similarity	NPD3640	Phase 3
0.8774	High Similarity	NPD3641	Approved
0.8377	Intermediate Similarity	NPD4664	Clinical (unspecified phase)
0.8176	Intermediate Similarity	NPD4584	Approved
0.815	Intermediate Similarity	NPD3534	Clinical (unspecified phase)
0.807	Intermediate Similarity	NPD5312	Approved
0.807	Intermediate Similarity	NPD5313	Approved
0.8061	Intermediate Similarity	NPD5977	Approved
0.8061	Intermediate Similarity	NPD5978	Approved
0.7895	Intermediate Similarity	NPD2898	Approved
0.7865	Intermediate Similarity	NPD7291	Discontinued
0.7831	Intermediate Similarity	NPD7298	Approved
0.7824	Intermediate Similarity	NPD6107	Approved
0.7819	Intermediate Similarity	NPD4859	Phase 1
0.7758	Intermediate Similarity	NPD4017	Approved
0.774	Intermediate Similarity	NPD2968	Approved
0.774	Intermediate Similarity	NPD2971	Approved
0.7697	Intermediate Similarity	NPD6618	Phase 2
0.7674	Intermediate Similarity	NPD4166	Phase 2
0.767	Intermediate Similarity	NPD6297	Approved
0.7665	Intermediate Similarity	NPD4773	Phase 2
0.7665	Intermediate Similarity	NPD4772	Phase 2
0.7636	Intermediate Similarity	NPD6030	Approved
0.7636	Intermediate Similarity	NPD6031	Approved
0.7613	Intermediate Similarity	NPD2669	Clinical (unspecified phase)
0.7605	Intermediate Similarity	NPD1337	Clinical (unspecified phase)
0.756	Intermediate Similarity	NPD7110	Phase 1
0.756	Intermediate Similarity	NPD7109	Clinical (unspecified phase)
0.754	Intermediate Similarity	NPD4107	Approved
0.7527	Intermediate Similarity	NPD4420	Approved
0.75	Intermediate Similarity	NPD6851	Approved
0.75	Intermediate Similarity	NPD6853	Approved
0.7486	Intermediate Similarity	NPD2488	Approved
0.7486	Intermediate Similarity	NPD2490	Approved
0.7457	Intermediate Similarity	NPD7201	Clinical (unspecified phase)
0.7425	Intermediate Similarity	NPD6662	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD4482	Phase 3
0.7396	Intermediate Similarity	NPD6876	Approved
0.7396	Intermediate Similarity	NPD6875	Approved
0.7389	Intermediate Similarity	NPD7132	Clinical (unspecified phase)
0.738	Intermediate Similarity	NPD2975	Approved
0.738	Intermediate Similarity	NPD5564	Approved
0.738	Intermediate Similarity	NPD2974	Approved
0.738	Intermediate Similarity	NPD2973	Approved
0.7371	Intermediate Similarity	NPD4010	Discontinued
0.7368	Intermediate Similarity	NPD5006	Approved
0.7368	Intermediate Similarity	NPD4585	Approved
0.7368	Intermediate Similarity	NPD5005	Approved
0.7368	Intermediate Similarity	NPD3057	Approved
0.7353	Intermediate Similarity	NPD6385	Approved
0.7353	Intermediate Similarity	NPD6386	Approved
0.7349	Intermediate Similarity	NPD3124	Discontinued
0.7345	Intermediate Similarity	NPD5602	Clinical (unspecified phase)
0.7342	Intermediate Similarity	NPD5718	Phase 2
0.7341	Intermediate Similarity	NPD1309	Phase 2
0.7341	Intermediate Similarity	NPD1307	Phase 2
0.7337	Intermediate Similarity	NPD824	Approved
0.7326	Intermediate Similarity	NPD7667	Clinical (unspecified phase)
0.7303	Intermediate Similarity	NPD8252	Approved
0.7303	Intermediate Similarity	NPD8099	Discontinued
0.7303	Intermediate Similarity	NPD8251	Approved
0.7297	Intermediate Similarity	NPD5525	Clinical (unspecified phase)
0.7288	Intermediate Similarity	NPD4481	Phase 3
0.7284	Intermediate Similarity	NPD6028	Clinical (unspecified phase)
0.7284	Intermediate Similarity	NPD6029	Clinical (unspecified phase)
0.7277	Intermediate Similarity	NPD3533	Approved
0.7277	Intermediate Similarity	NPD2972	Approved
0.7277	Intermediate Similarity	NPD3448	Approved
0.7277	Intermediate Similarity	NPD2491	Approved
0.7263	Intermediate Similarity	NPD4580	Approved
0.7263	Intermediate Similarity	NPD5457	Discontinued
0.7263	Intermediate Similarity	NPD8156	Discontinued
0.7251	Intermediate Similarity	NPD6873	Phase 2
0.7229	Intermediate Similarity	NPD5241	Discontinued
0.7225	Intermediate Similarity	NPD2493	Approved
0.7225	Intermediate Similarity	NPD3450	Approved
0.7225	Intermediate Similarity	NPD3452	Approved
0.7225	Intermediate Similarity	NPD2494	Approved
0.7216	Intermediate Similarity	NPD7802	Discontinued
0.7184	Intermediate Similarity	NPD6788	Approved
0.7168	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.7167	Intermediate Similarity	NPD3050	Clinical (unspecified phase)
0.7158	Intermediate Similarity	NPD7280	Phase 3
0.7158	Intermediate Similarity	NPD5917	Clinical (unspecified phase)
0.7158	Intermediate Similarity	NPD5071	Phase 2
0.7158	Intermediate Similarity	NPD7281	Phase 3
0.7151	Intermediate Similarity	NPD5089	Approved
0.7151	Intermediate Similarity	NPD5090	Approved
0.7135	Intermediate Similarity	NPD5242	Approved
0.7117	Intermediate Similarity	NPD6896	Approved
0.7117	Intermediate Similarity	NPD6895	Approved
0.7113	Intermediate Similarity	NPD4582	Approved
0.7113	Intermediate Similarity	NPD4583	Approved
0.7107	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7079	Intermediate Similarity	NPD6071	Discontinued
0.7071	Intermediate Similarity	NPD5676	Approved
0.7062	Intermediate Similarity	NPD4002	Approved
0.7062	Intermediate Similarity	NPD4004	Approved
0.7059	Intermediate Similarity	NPD3647	Clinical (unspecified phase)
0.7055	Intermediate Similarity	NPD2492	Phase 1
0.7045	Intermediate Similarity	NPD7831	Phase 2
0.7045	Intermediate Similarity	NPD7833	Phase 2
0.7045	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.7043	Intermediate Similarity	NPD4084	Clinical (unspecified phase)
0.7039	Intermediate Similarity	NPD2970	Approved
0.7039	Intermediate Similarity	NPD2969	Approved
0.7037	Intermediate Similarity	NPD3110	Approved
0.7037	Intermediate Similarity	NPD3109	Approved
0.7037	Intermediate Similarity	NPD3140	Approved
0.7037	Intermediate Similarity	NPD3142	Approved
0.7035	Intermediate Similarity	NPD7225	Discontinued
0.7029	Intermediate Similarity	NPD2563	Approved
0.7029	Intermediate Similarity	NPD2560	Approved
0.7027	Intermediate Similarity	NPD8054	Approved
0.7027	Intermediate Similarity	NPD8053	Approved
0.7015	Intermediate Similarity	NPD8149	Discontinued
0.701	Intermediate Similarity	NPD956	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD2489	Approved
0.7	Intermediate Similarity	NPD1754	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD27	Approved
0.6995	Remote Similarity	NPD7255	Clinical (unspecified phase)
0.6983	Remote Similarity	NPD3051	Approved
0.6982	Remote Similarity	NPD6783	Clinical (unspecified phase)
0.698	Remote Similarity	NPD5980	Discovery
0.6968	Remote Similarity	NPD7235	Clinical (unspecified phase)
0.6964	Remote Similarity	NPD6658	Clinical (unspecified phase)
0.6961	Remote Similarity	NPD6720	Clinical (unspecified phase)
0.6961	Remote Similarity	NPD7858	Clinical (unspecified phase)
0.6944	Remote Similarity	NPD6688	Approved
0.6944	Remote Similarity	NPD6687	Approved
0.6939	Remote Similarity	NPD4040	Phase 1
0.6936	Remote Similarity	NPD7261	Clinical (unspecified phase)
0.6932	Remote Similarity	NPD5967	Approved
0.6932	Remote Similarity	NPD5616	Clinical (unspecified phase)
0.6931	Remote Similarity	NPD7668	Phase 2
0.6927	Remote Similarity	NPD7907	Approved
0.6923	Remote Similarity	NPD5307	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD5084	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD2822	Clinical (unspecified phase)
0.6919	Remote Similarity	NPD1670	Discontinued
0.6901	Remote Similarity	NPD1424	Approved
0.6889	Remote Similarity	NPD5183	Approved
0.6889	Remote Similarity	NPD5186	Approved
0.6882	Remote Similarity	NPD4078	Clinical (unspecified phase)
0.6854	Remote Similarity	NPD6533	Clinical (unspecified phase)
0.6854	Remote Similarity	NPD8005	Clinical (unspecified phase)
0.685	Remote Similarity	NPD4997	Clinical (unspecified phase)
0.6848	Remote Similarity	NPD2653	Approved
0.6845	Remote Similarity	NPD3655	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD2421	Approved
0.6842	Remote Similarity	NPD2420	Approved
0.6839	Remote Similarity	NPD4005	Discontinued
0.6839	Remote Similarity	NPD3866	Clinical (unspecified phase)
0.6829	Remote Similarity	NPD4665	Approved
0.6829	Remote Similarity	NPD4111	Phase 1
0.6823	Remote Similarity	NPD7669	Phase 3
0.6823	Remote Similarity	NPD4413	Clinical (unspecified phase)
0.6821	Remote Similarity	NPD7501	Clinical (unspecified phase)
0.6818	Remote Similarity	NPD7248	Discontinued
0.6818	Remote Similarity	NPD7607	Clinical (unspecified phase)
0.6809	Remote Similarity	NPD5087	Clinical (unspecified phase)
0.6807	Remote Similarity	NPD743	Approved
0.6806	Remote Similarity	NPD7296	Approved
0.6791	Remote Similarity	NPD6146	Clinical (unspecified phase)
0.6789	Remote Similarity	NPD5896	Clinical (unspecified phase)
0.6789	Remote Similarity	NPD6377	Clinical (unspecified phase)
0.6788	Remote Similarity	NPD6834	Approved
0.6784	Remote Similarity	NPD7124	Phase 2
0.6784	Remote Similarity	NPD3845	Phase 1
0.6778	Remote Similarity	NPD5677	Discontinued
0.6774	Remote Similarity	NPD5536	Phase 2
0.6771	Remote Similarity	NPD6181	Discontinued
0.6768	Remote Similarity	NPD4475	Approved
0.6768	Remote Similarity	NPD2674	Phase 3
0.6768	Remote Similarity	NPD554	Clinical (unspecified phase)
0.6768	Remote Similarity	NPD4474	Approved
0.6758	Remote Similarity	NPD2388	Discontinued
0.6757	Remote Similarity	NPD5900	Clinical (unspecified phase)
0.6754	Remote Similarity	NPD3808	Clinical (unspecified phase)
0.6753	Remote Similarity	NPD7034	Discontinued
0.6744	Remote Similarity	NPD5297	Approved
0.6744	Remote Similarity	NPD7048	Phase 3
0.6742	Remote Similarity	NPD5353	Approved
0.6735	Remote Similarity	NPD6612	Phase 2
0.6724	Remote Similarity	NPD7427	Discontinued
0.6723	Remote Similarity	NPD7577	Discontinued
0.6723	Remote Similarity	NPD6844	Discontinued
0.672	Remote Similarity	NPD6996	Clinical (unspecified phase)
0.6719	Remote Similarity	NPD3922	Approved
0.6719	Remote Similarity	NPD3924	Approved
0.6719	Remote Similarity	NPD3923	Approved
0.6719	Remote Similarity	NPD3921	Approved
0.6706	Remote Similarity	NPD5177	Phase 3
0.6705	Remote Similarity	NPD3688	Clinical (unspecified phase)
0.6705	Remote Similarity	NPD3146	Approved
0.6703	Remote Similarity	NPD6747	Phase 1
0.6703	Remote Similarity	NPD5521	Clinical (unspecified phase)
0.6702	Remote Similarity	NPD7311	Approved
0.6702	Remote Similarity	NPD7312	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